Levofloxacin-based rescue regimens after Helicobacter pylori treatment failure: how strong is the evidence?
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Anti-Bacterial Agents↗
Biomedical subjects
R H Hunt
Publications and source records attributed to R H Hunt.
Dieldrin resistance in the malaria vector Anopheles gambiae in Ghana.
Anopheles gambiae Giles s.s. (Diptera: Culicidae) is one of the principal vectors of malaria in the Ashanti region of central Ghana. High levels of resistance to dieldrin were recorded in a wild-caught sample from Obuasi (south of Kumasi) as well as a laboratory colony established using material from the wild population. Cytogenetic analysis of wild-caught and laboratory samples revealed chromosomal polymorphism for inversions 2La and 2Rb. Although inversion 2La has previously been shown to be associated with dieldrin resistance in certain other laboratory strains originating from West Africa, there was no obvious association between inversion karyotype assortment and the resistance phenotype in the Obuasi population. In addition, polymerase chain reaction analysis indicated the presence of the alanine296 to glycine mutation in the GABA (gamma amino-butyric acid) receptor (which has been mapped to a chromosomal position within inversion 2La). This mutation has previously been shown to be associated with dieldrin resistance in the same An. gambiae laboratory strains of West African origin. Our data show only a weak association between the dieldrin resistance phenotype and the presence of this mutation, suggesting that another dieldrin resistance mechanism is operational in the Obuasi population. Biochemical and synergist exposure assays suggest a metabolic component, probably mediated by monooxygenase P450 enzymes. We conclude that dieldrin resistance in the An. gambiae population of the Obuasi region occurs at a high level - most likely in the absence of selection - and that control of the resistance phenotype is polyfactorial and must include components other than mutations in the GABA receptor locus.
Animals↗
Review article: the unmet needs in delayed-release proton-pump inhibitor therapy in 2005.
Proton-pump inhibitors have been highly effective in managing acid-related gastrointestinal disorders, but challenges remain. This paper reviews the challenges in the management of patients with gastro-oesophageal symptoms who do not respond adequately to proton-pump inhibitor therapy; the treatment of patients with non-variceal upper gastrointestinal bleeding; the prevention of stress-related mucosal bleeding; the treatment and prevention of non-steroidal anti-inflammatory drug-related gastrointestinal injury; and the optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection, all of which represent unmet clinical needs. Antisecretory therapy with a rapid onset of action and sustained antisecretory effect may help to address some of the unmet needs discussed, especially in the management of gastro-oesophageal reflux disease, non-variceal upper gastrointestinal bleeding and non-steroidal anti-inflammatory drug-related gastrointestinal complications.
Anti-Inflammatory Agents, Non-Steroidal↗
Laboratory selection for and characteristics of pyrethroid resistance in the malaria vector Anopheles funestus.
A laboratory colony of Anopheles funestus Giles (Diptera: Culicidae) was established in 2000 from material collected from southern Mozambique where pyrethroid resistance had been demonstrated in the wild population. A subsample of the colony was selected for pyrethroid resistance using 0.1% lambda-cyhalothrin. Bioassay susceptibility tests in subsequent generations F(2) to F(4) showed increased resistance with each successive generation. Survival of individual mosquitoes fed only on 10% sugar solution, increased with age up to 4 days, but by day 10 had decreased significantly. However, females that had been mated and given bloodmeals showed no such increase in mortality with age. Biochemical analysis of resistant and susceptible individuals showed increased monooxygenase and glutathione S-transferase activity but no significant correlation with age of the mosquitoes.
Aging↗
Evaluation of a species-specific PCR assay for the Anopheles funestus group from eleven African countries and Madagascar.
A newly published cocktail polymerase chain reaction (PCR) assay can identify five members of the Anopheles funestus group: An. funestus, An. vaneedeni, An. parensis, An. leesoni and An. rivulorum. The assay was evaluated on specimens from 11 African countries: Angola, Cote d'Ivoire, Ethiopia, Kenya, Malawi, Mozambique, Namibia, South Africa, Tanzania, Uganda and Zambia; and the island of Madagascar. The polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and the internal transcribed spacer PCR (ITS2-PCR) assays were used as a priori identification methods on 900 specimens. Of these, 96.4% were correctly identified using the new cocktail PCR method. The remaining 3.5% (32) from Malawi failed to amplify. The failure to identify these samples was not significantly different from the samples from the other countries (Chi-square; P > 0.05). The results suggest that the new species-specific PCR assay is an efficient and effective means of identifying 5 members of the An. funestus group in a single reaction. It is also less time-consuming than the molecular methods previously used on the group.
Africa↗
Establishment of T-Helper-2 immune response based gerbil model of enteric infection.
BACKGROUND: The reciprocal antagonism of T-helper-1 (Th-1) and Th-2 type immune responses suggests that helminth parasitic infection may ameliorate disease where a Th-1 type response dominates. The Mongolian gerbil has been useful in the investigation of the pathogenesis of gastric cancer, since long-term infection of gerbils with Helicobacter pylori induces adenocarcinoma. In this study the kinetics of worm expulsion and associated immune responses in gerbils infected with Trichinella spiralis were investigated in an attempt to establish an animal model of parasitic infection that could be helpful when investigating the effect of a Th-2 type response on Th-1-based intestinal disorders. METHODS: Gerbils were infected with various doses of infective T. spiralis larvae and were euthanized on different days after infection to investigate the intestinal worm recovery, goblet cell population, eosinophil response and serum IgG1 responses. RESULTS: The number of worms recovered from the intestine was dependent on the number of larvae used for the infection. Almost all worms were expelled spontaneously by day 26 post-infection, when the gerbils had been infected with 375 or 750 larvae. The number of intestinal goblet cells, eosinophils and the serum IgG1 level significantly increased following infection compared with the control. CONCLUSION: This is the first comprehensive report on the time-course of T. spiralis infection in gerbils. The data indicate that the T. spiralis-infected gerbil could be used as a model of the Th-2-based response to investigate the effect of a parasite-induced Th-2 response on various Th-1-mediated intestinal disorders such as H. pylori-induced gastritis and gastric carcinoma.
Animals↗
Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing.
Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can each result in gastric or duodenal ulcer(s) and ulcer complications. Together, H. pylori infection and NSAIDs account for approximately 90% of peptic ulcer disease. In 2003, the results of studies suggest, and guidelines recommend, the careful selection of anti-inflammatory drugs - NSAIDs or selective COX-2 inhibitors (coxibs) based upon patients gastrointestinal history and use of aspirin therapy. Testing for, and cure of, H. pylori infection is recommended in patients prior to the initiation of NSAID therapy and in those who are currently receiving NSAIDs and have a history of dyspepsia, peptic ulcer or ulcer complications. For patients who present with peptic ulcer bleeding but require NSAIDs long-term, H. pylori eradication therapy should be considered, followed by continuous proton pump inhibitor prophylaxis to prevent re-bleeding, regardless of which kind of NSAID (nonselective NSAID /coxib) is being prescribed. Routine testing for, and eradication of, H. pylori infection has not been recommended for current takers of NSAIDs with no or low risk of complications. The management of patients taking low-dose aspirin is complex, but eradication of H. pylori infection alone in those with a past history of bleeding does not guarantee complete protection and therefore a proton pump inhibitor should also be given. The success of eradication therapy should always be confirmed, because of the risk of ulcer recurrence and bleeding in H. pylori-infected patients who require anti-inflammatory treatments.
Anti-Inflammatory Agents, Non-Steroidal↗
Effect of Th1 cytokines on acid secretion in pharmacologically characterised mouse gastric glands.
BACKGROUND AND AIMS: Acid secretion plays an important role in the ecology of Helicobacter species and acid secretory status heralds patterns of gastritis. The presence of inflammatory cells and their products, in close proximity to parietal cells, questions the extent of the effect of cytokines on acid secretion. METHODS: We adopted and extensively characterised the mouse gastric gland preparation and its secretory capacity, which was measured using (14)C-aminopyrine accumulation. Subsequently, we tested the secretory properties of a wide range of species specific cytokines, including those associated with Th1 and Th2 immune responses. RESULTS: (14)C-aminopyrine accumulation in mouse gastric glands was shown to be a very sensitive "in vitro" method of testing classical secretagogues and antisecretory compounds, and provided pharmacological data on acid secretion in the mouse. Only two mouse cytokines, interleukin 2 and interferon gamma, had a direct effect on acid secretion causing dose dependent inhibition. CONCLUSIONS: Both cytokines belong to the Th1 type immune response and consequently their inhibitory effect may play a role in the hyposecretion seen with H pylori infection and colonisation throughout the corpus of the stomach that potentially can lead to gastric atrophy and subsequently, in some cases, cancer.
Aminopyrine↗
Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib.
BACKGROUND: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. AIM: To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. RESULTS: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of > or = 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of > or = 5 mm. CONCLUSIONS: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.
Adolescent↗
Anopheles arabiensis and An. quadriannulatus resistance to DDT in South Africa.
The malaria control programme of KwaZulu-Natal Province, South Africa, includes Mamfene and Mlambo communities. Western-type houses there are currently sprayed with deltamethrin, whereas traditional houses are sprayed with DDT for malaria control. In 2002, mosquitoes of the Anopheles gambiae complex (Diptera: Culicidae) were collected from DDT-sprayed houses, by window exit traps, and from man-baited nets outdoors. Larval collections were also carried out at Mzinweni Pan near Mlambo. Species of the An. gambiae complex were identified by rDNA polymerase chain reaction assay. The majority of samples collected by window trap and baited nets were identified as the malaria vector An. arabiensis Patton, with a few An. merus Dönitz and An. quadriannulatus (Theobald). The larval collections were predominantly An. quadriannulatus with a small number of An. arabiensis. Standard WHO insecticide susceptibility tests using 4% DDT and 0.05% deltamethrin were performed on both wild-caught females and laboratory-reared progeny from wild-caught females. Wild-caught An. arabiensis samples from window traps gave 63% and 100% mortality 24-h post-exposure to DDT or deltamethrin, respectively. Wild-caught An. arabiensis samples from man-baited net traps gave 81% mortality 24-h post-exposure to DDT. The F1 progeny from 22 An. arabiensis females showed average mortality of 86.5% 24-h post-exposure to DDT. Less than 80% mortality was recorded from five of these families. Biochemical analyses of samples from each of the families revealed comparatively high levels of glutathione-S-transferases and non-specific esterases in some families, but without significant correlation to bioassay results. Wild-caught An. quadriannulatus larvae were reared through to adults and assayed on 4% DDT, giving 47% (n = 36) mortality 24-h post-exposure. Finding DDT resistance in the vector An. arabiensis, close to the area where we previously reported pyrethroid-resistance in the vector An. funestus Giles, indicates an urgent need to develop a strategy of insecticide resistance management for the malaria control programmes of southern Africa.
Africa, Southern↗
Acid suppression in healthy subjects following lansoprazole or pantoprazole.
AIM: To compare the effect of lansoprazole, 30 mg once daily, with that of pantoprazole, 40 mg once daily, for the inhibition of gastric acid secretion. METHODS: Two randomized, single-blind, two-way, crossover studies were conducted in 74 healthy male volunteers. Lansoprazole, 30 mg, or pantoprazole, 40 mg, was administered once daily for five consecutive days with at least a 2-week washout period between regimens. Ambulatory 24-h intragastric pH was recorded at baseline and on days 1 and 5 of each crossover treatment period. RESULTS: On day 1 in both studies, lansoprazole, 30 mg, produced significantly higher mean 24-h intragastric pH values when compared to pantoprazole, 40 mg (3.78 vs. 3.08, P < 0.001, and 3.97 vs. 3.20, P < 0.001, in the first and second studies, respectively). In both studies, lansoprazole, 30 mg, produced significantly greater proportions of time that the intragastric pH was above 3, 4 and 5 when compared with pantoprazole, 40 mg (P < 0.005 in all comparisons). By treatment day 5 in the first study, lansoprazole, 30 mg, continued to produce a higher mean 24-h intragastric pH (4.15 vs. 3.91, P=0.014) and a significantly greater percentage of time that the intragastric pH was above 4 (63% vs. 56%, P=0.017) and 5 (41% vs. 30%, P < 0.001) when compared with pantoprazole, 40 mg. In the second study, the effects on intragastric pH were comparable between the two treatment groups. Headache was the most commonly reported adverse experience (nine lansoprazole-treated subjects, seven in the first study and two in the second study; six pantoprazole-treated subjects, five in the first study and one in the second study). CONCLUSIONS: Lansoprazole, 30 mg once daily, produces a faster onset and greater degree of acid inhibition than pantoprazole, 40 mg once daily. The implications for these differences on symptom relief and healing of erosive oesophagitis should be explored.
2-Pyridinylmethylsulfinylbenzimidazoles↗
PCR assay for identification of Anopheles quadriannulatus species B from Ethiopia and other sibling species of the Anopheles gambiae complex.
Sibling species A and B of Anopheles quadriannulatus (Theobald) are recognized as allopatric members of the Anopheles gambiae Giles complex of Afrotropical mosquitoes (Diptera: Culicidae). Species A represents An. quadriannulatus sensu stricto, widespread in southern Africa, whereas An. quadriannulatus species B occurs in Ethiopia. Because of difficulty of identification, distribution of An. quadriannulatus sensu lato remains poorly known. Cytotaxonomy and the standard DNA polymerase chain reaction (PCR) assay do not distinguish between species A and B of An. quadriannulatus. By optimizing the standard PCR assay (Scott et al., 1993) for identification of members of the An. gambiae complex, we identified two discriminant fragments of 153 bp and 900 bp from DNA of An. quadriannulatus species B, whereas only the 153 bp fragment was amplified for species A from South Africa. This modified PCR assay can therefore be used to distinguish between species A and B of An. quadriannulatus s.l. as well as other members of the An. gambiae complex.
Africa, Southern↗
Dynamics of the malaria-vector populations in coastal Lagos, south-western Nigeria.
An entomological study was carried out in coastal Lagos, south-western Nigeria, to explore the role of Anopheles gambiae s.l. and An. moucheti in the transmission of Plasmodium falciparum in this holo-endemic area. Mosquitoes were caught, on human bait at night and by pyrethrum-spray catches during the day, twice a month throughout 2000. Of the 1812 Anopheles mosquitoes collected, An. gambiae s.l., the predominant vector species, represented 78.7% while the other 21.3% were An. moucheti. The results of a PCR-based test identified 56.8% of the mosquitoes of the An. gambiae complex collected as An. gambiae s.s., 36.9% as An. melas and 6.3% as An. arabiensis. Anopheles gambiae s.s. was predominantly recorded in the wet season, biting females being collected from May to October, with a peak in July. Anopheles melas and An. moucheti were present throughout the year-long study whereas An. arabiensis was mainly found in the dry season. The results of ELISA-based analyses of bloodmeals indicated that An. gambiae s.s., An. melas and An. moucheti were predominantly anthropophagic whereas An. arabiensis was largely zoophagic. Among all of the females investigated, 3.6% of the An. gambiae s.s., 1.9% of the An. melas, 1.8% of the An. moucheti and 0% of the An. arabiensis were found to be infected with P. falciparum (i.e. carrying the parasite's circumsporozoite antigen). The corresponding proportions for the females collected during the dry season were 1.3%, 2.3%, 2.7% and 0%. The entomological inoculation rates for An. melas and An. moucheti were significantly higher during the dry season than at other times of the year. Taken together, these results indicate that An. melas and An. moucheti maintain transmission of P. falciparum during the dry season, while the biting population ofAn. gambiae s.s. is relatively small.
Animals↗
Resistance of the malaria vector Anopheles gambiae s.s. to pyrethroid insecticides, in south-western Nigeria.
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Animals↗
Stable chromosomal inversion polymorphisms and insecticide resistance in the malaria vector mosquito Anopheles gambiae (Diptera: Culicidae).
Anopheles gambiae Giles has been implicated as a major vector of malaria in Africa. A number of paracentric chromosomal inversions have been observed as polymorphisms in wild and laboratory populations of this species. These polymorphisms have been used to demonstrate the existence of five reproductive units in West African populations that are currently described as incipient species. They have also been correlated with various behavioral characteristics such as adaptation to aridity and feeding preference and have been associated with insecticide resistance. Two paracentric inversions namely 2La and 2Rb are highly ubiquitous in the wild and laboratory populations sampled. Both inversions are easily conserved during laboratory colonization of wild material and one shows significant positive heterosis with respect to Hardy-Weinberg proportions. Inversion 2La has previously been associated with dieldrin resistance and inversion 2Rb shows an association with DDT resistance based on this study. The stability and maintenance of these inversions as polymorphisms provides an explanation for the transmission and continued presence of DDT and dieldrin resistance in a laboratory strain of An. gambiae in the absence of insecticide selection pressure. This effect may also be operational in wild populations. Stable inversion polymorphism also provides a possible mechanism for the continual inheritance of suitable genetic factors that otherwise compromise the fitness of genetically modified malaria vector mosquitoes.
Animals↗
A cocktail polymerase chain reaction assay to identify members of the Anopheles funestus (Diptera: Culicidae) group.
Anopheles funestus Giles is a major malaria vector in Africa belonging to a group of species with morphologically similar characteristics. Morphological identification of members of the A. funestus group is difficult because of overlap of distinguishing characteristics in adult or immature stages as well as the necessity to rear isofemale lines to examine larval and egg characters. A rapid rDNA polymerase chain reaction (PCR) method has been developed to accurately identify five members of the A. funestus group. This PCR is based on species-specific primers in the ITS2 region on the rDNA to identify A. funestus (approximately 505bp), Anopheles vaneedeni Gillies and Coetzee (approximately 587bp), Anopheles rivulorum Leeson (approximately 411bp), Anopheles leesoni Evans (approximately 146bp), and Anopheles parensis Gillies (approximately 252bp).
Africa↗
Statistical learning in a serial reaction time task: access to separable statistical cues by individual learners.
The ability of adult learners to exploit the joint and conditional probabilities in a serial reaction time task containing both deterministic and probabilistic information was investigated. Learners used the statistical information embedded in a continuous input stream to improve their performance for certain transitions by simultaneously exploiting differences in the predictability of 2 or more underlying statistics. Analysis of individual learners revealed that although most acquired the underlying statistical structure veridically, others used an alternate strategy that was partially predictive of the sequences. The findings show that learners possess a robust learning device well suited to exploiting the relative predictability of more than I source of statistical information at the same time. This work expands on previous studies of statistical learning, as well as studies of artificial grammar learning and implicit sequence learning.
Adult↗
Repellent effects on Anopheles arabiensis biting humans in Kruger Park, South Africa.
Distribution of biting sites on the human body by the malaria vector Anopheles arabiensis Patton (Diptera: Culicidae) was investigated near a source of mosquitoes in the Kruger National Park, South Africa. Eight adult male volunteers (2 teams x 2 pairs of subjects) conducted human bait collections while seated on camp chairs in the open-air, wearing only short trousers (no shirt, socks or shoes). Mosquito collections during 18.30-22.30 hours on five consecutive nights in April 1998 yielded a total of 679 An. arabiensis females biting subjects with or without their ankles and feet treated with deet insect repellent (15% diethyl-3-methylbenzamide, Tabard lotion). On subjects whose feet and ankles were smeared with repellent, 160 An. arabiensis females were captured biting in 60 manhours: 88.1% on the legs, 1.4% on the arms and 1.2% on other parts of the body, but none on the repellent-treated feet or ankles. On subjects without repellent treatment, 519 An. arabiensis were caught biting in 60 man-hours: 81.1% on feet and ankles, 16.4% on legs, 1.4% on arms and 1.2% on the rest of the body. For individual subjects, the reduction of An. arabiensis bites ranged from 36.4 to 78.2% (mean protection 69.2%). Results of this study confirm previous findings that, in this part of South Africa - inhabited only by wildlife - when people sit outside during the evening An. arabiensis prefers to bite their lower limbs: 97.5% below the knees. Overall, the number of bites by the malaria vector An. arabiensis was reduced more than three-fold (from 26 to 8/person/evening), simply by treating ankles and feet with a consumer brand of deet repellent. Whether or not this provides a satisfactory degree of protection against malaria risk would depend on the malaria sporozoite rate in the malaria vector population.
Adult↗