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Biomedical subjects

J Curtis

Publications and source records attributed to J Curtis.

At least 55 records · Page 3Linked to original sources
PubMed1999

Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children.

In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.

Alleles↗
PubMed1999

Studies on anti-folate antimalarials in east Africa.

Chlorproguanil-dapsone (CD) appears to be a promising anti-folate combination (Amukoye et al., 1997) to substitute for pyrimethamine-sulfadoxine (PS), which has a long half-life and against which there is resistance in several Plasmodium falciparum populations including the highly endemic lowland area near Muheza, Tanzania (Trigg et al., 1997).

Africa, Eastern↗
PubMed1998

Surgical epidemic

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Journal Article↗
PubMed1998

Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion.

With the spread of resistance to chloroquine, the combination of sulphadoxine and pyrimethamine is growing in importance for the treatment of infection with the malaria parasite Plasmodium falciparum. Mutations in the dhfr gene of P. falciparum have been associated with resistance to pyrimethamine. Recently, several polymorphisms have been identified in the P. falciparum dhps gene which may correlate with sulphadoxine-resistance. Simple and rapid tests have been developed to detect these polymorphisms, using PCR followed by restriction digestion. These tests can accurately identify all the polymorphisms described to date at codons 16, 51, 59, 108, and 164 in the dhfr gene and those at codons 436, 437, 540, 581, and 613 in the dhps gene. A nested system has been developed which allows the accurate detection of these polymorphisms in samples of fingerprick blood collected on glass fiber membranes and filter papers, some with very low parasitaemias.

Animals↗
PubMed1998

Antileukemic action of buthionine sulfoximine: evidence for an intrinsic death mechanism based on oxidative stress.

The glutathione-depleting agent buthionine sulfoximine (BSO) was found to be toxic to some AML blast populations. This toxicity was manifested as the appearance of high levels of reactive oxygen generation in GSH-depleted cells, and later by the loss of mitochondrial membrane potential and an increase in intracellular calcium. Striking heterogeneity in BSO sensitivity was observed in a series of four human AML cell lines, and in fresh leukemic blasts obtained from eight AML patients. In some cases, toxicity was seen at BSO concentrations as low as 1 microM; approximately 100-fold less than the plasma levels achieved in patients treated with BSO as a drug resistance reversing agent. Based on these results we propose that some AML blast populations are unusually dependent on GSH-based antioxidant mechanisms, due to high intrinsic rates of reactive oxygen generation. The mitochondrial respiratory chain is the most likely source of this reactive oxygen. Because toxicity is seen at clinically achievable concentrations of BSO, this agent might have antileukemic activity in patients.

Adult↗
PubMed1998

Polymorphisms in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes of Plasmodium falciparum and in vivo resistance to sulphadoxine/pyrimethamine in isolates from Tanzania.

The efficacy of sulphadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Africa is increasingly compromised by development of resistance. The occurrence of mutations associated with the active site sequence in the Plasmodium falciparum genes coding for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) is associated with in vitro resistance to pyrimethamine and sulphadoxine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results show that alleles of DHPS (436-alanine, 437-alanine and 540-lysine) were significantly reduced in prevalence on day 7 after S/P treatment. In this area, a DHPS with 436-serine, 437-glycine and 540-glutamate appears to play a major role in resistance to S/P in vivo. Evidence for the influence of mutations in the DHFR gene in this investigation is not clear, probably because of the high prevalence of 'resistance-related' mutations at day 0 in the local parasite population. For apparently the same reason, it was not possible to show a statistical association between S/P resistance and the presence of particular polymorphisms in the DHFR and DHPS genes before treatment.

Animals↗
PubMed1998

In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment.

Plasmodium falciparum present in blood samples collected before and 3 weeks after treatment with either pyrimethamine-sulfadoxine or chlorproguanil-dapsone was analyzed for variants of the genes coding for the target enzymes of antifolate drugs, dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Fragments of the genes were amplified by polymerase chain reactions, and variants were identified by specific restriction endonuclease digestion. Treatment with either drug combination selected for the variants Ile51, Arg59, and Asn108 of DHFR, which have been associated with in vitro resistance to pyrimethamine and cycloguanil. The genotype Ser436, Gly437, and Glu540 of DHPS was selected by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment, showing that a combination of these three variants is important for in vivo resistance to sulfadoxine in the area studied.

Amino Acid Sequence↗
PubMed1998

Intraspecific variation in the rDNA its loci of 37-collar-spined echinostomes from North America: implications for sequence-based diagnoses and phylogenetics.

The recent finding of the 37-collar-spined Echinostoma revolutum in North America prompted rDNA nucleotide sequence comparisons between this worm and the sympatric Echinostoma trivolvis. Three isolates of E. revolutum from distinct sites and 2 isolates of E. trivolvis collected from a single site were used in this analysis. Sequence data were compared to those from previously sequenced members of the 37-collar-spine group. The 3 North American isolates of E. revolutum were found to be identical, but they differed from Eurasian isolates of E. revolutum at 9 of the 1,006 sites sequenced. Further, 1 of the E. trivolvis isolates studied herein was identical to the published sequence for this species, but 6 nucleotide changes were observed in the second E. trivolvis isolate. Restriction fragment length polymorphisms at this locus support the nucleotide differences found between the E. trivolvis isolates. The degree of intraspecific variation detected raises questions regarding the utility of the internal-transcribed spacer regions of the ribosomal DNA repeat for taxonomic diagnosis and in phylogenetic studies for poorly differentiated groups, such as the 37-collar-spined congeners.

Animals↗
PubMed1997

Gender and perceived pay entitlement: testing for effects of experience with income.

This article reports on 2 studies where variations on a research design from the literature on gender and perceived pay entitlement were used to test for effects of past pay experience and salience of the pay experience for the participants. In Study 1, level of previous income was not a predictor of self-payment behavior for women or men, and men allocated more pay to themselves than did women. In Study 2, women and men did not differ on perceived entitlement when the income and work experience were made salient, but they did in the nonsalient condition, as in Study 1. Also, past income and self-pay were positively correlated for women in the salient condition. Further, when the data from Study 1 and Study 2 from the same condition (past income nonsalient) were combined, those with the higher previous income level paid themselves more than others, among both men and women.

Analysis of Variance↗
PubMed1997

High prevalence of mutations in the dihydrofolate reductase gene of Plasmodium falciparum in isolates from Tanzania without evidence of an association to clinical sulfadoxine/pyrimethamine resistance.

Recently the efficacy of sulfadoxine/pyrimethamine (S/P) in treatment of uncomplicated falciparum malaria in Tanzania has been seriously compromised by the development of resistance. The occurrence of active site mutations in the Plasmodium falciparum gene sequence coding for dihydrofolate reductase (DHFR) is known to confer resistance to pyrimethamine. This study investigates the occurrence of these mutations in infected blood samples taken from Tanzanian children before treatment with S/P and their relationship to parasite breakthrough by day 7. The results confirm the occurrence of one or more DHFR mutations in all the samples, but no relationship was found with the presence of parasites in the blood at day 7. The results suggest that alterations in the coding region for dihydropteroate synthetase (DHPS), the enzyme target for sulfadoxine, should be studied in order to predict resistance to the S/P combination. It has been proposed earlier that sulfadoxine could itself act on DHFR, because of a false dihydrofolate produced by drug metabolism through DHPS and dihydrofolate synthase. The results of this treatment study suggest that such a possibility is unlikely.

Animals↗
PubMed1996

Ethical considerations in the management of asylum seekers on hunger strike.

Hunger strikes have confronted physicians with complex ethical dilemmas throughout history. Asylum seekers under threat of forced repatriation have emerged as a new category of hunger strikers, posing novel challenges for management. The management of 3 Cambodian asylum seekers on hunger strike admitted to a hospital in Sydney, New South Wales, Australia, posted important ethical dilemmas for the physicians and mental health experts involved in their care. Several factors confounded the task of assessment and decision making, including language and cultural barriers, the patients' past exposure to persecution by authorities, and the complexities of the legal procedures being pursued. Different rules appeared to govern the actions of the hunger strikers, the medical team, and the immigration authorities, creating a ¿malignant triangle¿ of mounting confrontation. Recent recommendations for the management of asylum-seeking hunger strikers include the appointment of an external physician of confidence and the writing of a confidential advance directive specifying the hunger striker's wishes about resuscitation in the event of collapse. In addition, we consider the value of constituting an ad hoc ethics committee to advise the responsible physician on points of conflict in managing the hunger strike. The advantages and limitations of these proposals in relation to the particular cultural, historical, and contextual issues relevant to asylum seekers are examined herein.

Advance Directives↗
PubMed1996

Alpha-interferon and pregnancy in a patient with CML.

A 34-year-old woman on interferon for CML for 7 years, experienced problems with conception. Full work-up revealed a short luteal phase and therapy with clomiphene was initiated. Pregnancy occurred and a normal infant was delivered by C-section. The detailed infertility evaluation is described and the impact of interferon therapy on pregnancy is reviewed. Successful pregnancy appears possible in woman taking interferon on a chronic basis.

Adult↗
PubMed1996

Production of pulmonary vasodilation by tolazoline, independent of nitric oxide production in neonatal lambs.

OBJECTIVE: To determine whether tolazoline reduces pulmonary vascular resistance (PVR) by means of endogenous nitric oxide production. DESIGN: Thirty newborn lambs (2 to 7 days of age) were anesthetized with pentobarbital, and their lungs were ventilated through an endotracheal tube. Intravascular catheters were placed in the left ventricle, descending aorta, right atrium, and pulmonary artery for continuous monitoring of intravascular pressures. Cardiac output was measured with radiolabeled microspheres. Arterial carbon dioxide pressure and pH were maintained in a normal range throughout the experiments. Animals were randomly assigned to the following groups: group 1, lungs ventilated with a hypoxic gas mixture and administered tolazoline; group 2, given N omega-nitro-L-arginine (L-NA) (5 mg/min intravenously for 60 minutes) and tolazoline; group 3, given L-NA with hypoxia and tolazoline. Acetylcholine (0.5 microgram/kg) was injected into the right atrium to assess pulmonary nitric oxide synthase activity before and after the L-NA infusion. Data were analyzed by analysis of variance. RESULTS: L-NA inhibited the acetylcholine-induced reduction in mean pulmonary artery pressure (MPAP) by more than 75%. Hypoxia and L-NA increased both MPAP and PVR. Tolazoline produced immediate reductions in both MPAP and PVR in all three groups (group 1, 27% +/- 3% and 50% +/- 5%; group 2, 34% +/- 5% and 50% +/- 6%; and group 3, 31% +/- 4% and 46% +/- 5%, respectively). CONCLUSIONS: These results suggest that tolazoline produces vasodilation independent of nitric oxide production. Understanding the mechanism by which tolazoline produces pulmonary vasodilation may provide insight into the clinical use of this drug and information regarding other potential endogenous mediators of pulmonary vasomotor tone in the neonate.

Animals↗
PubMed1996

Subchronic use of the St. Jude centrifugal pump as a mechanical assist device in calves.

The purpose of this experiment was to study the effects of the St. Jude Lifestream centrifugal pump on hemodynamic and hematologic parameters and the incidence of postmortem findings in a subchronic ex vivo left ventricular assist animal model. Five calves were implanted with the pump as a left ventricular assist device (left atrial to thoracic aorta bypass) and studied for 96 h of continuous pumping under identical conditions. Heparin (100 IU/kg) was administered only in the initial saline pump prime. Throughout the protocol, mean arterial and central venous pressures averaged 102.1 +/- 4.6 and 3.4 +/- 2.2 mm Hg, respectively. Pump flow was 47.8 +/- 8.4 ml/kg/min at a mean pump speed of 1,676.3 +/- 106.1 rpm. No clinical abnormalities or mechanical malfunctions attributable to the pump were detected during the 96 h of continuous pumping for each calf. Mean plasma-free hemoglobin after 96 h was 3.9 +/- 3.7 mumol/L (p = 0.337 compared to baseline). At post mortem, renal infarctions were detected in 1 calf. No other pump-associated lesions were detected in any of the other calves. We have concluded that the St. Jude Lifestream centrifugal pump functions reliably during 96 h of continuous left heart bypass in a calf model.

Animals↗