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Biomedical subjects

M Rowland

Publications and source records attributed to M Rowland.

At least 19 recordsLinked to original sources

Routine mobilization of the splenic flexure is not necessary during anterior resection for rectal cancer.

PURPOSE: Splenic flexure mobilization is widely considered to be an essential component of anterior resection for rectal cancer. It was our hypothesis that selective splenic flexure mobilization would reduce operative times without increasing morbidity or affecting cure. METHODS: A total of 100 consecutive patients with rectal cancer (mean 8 (range, 4-15) cm from anal verge) who underwent anterior resection for cure between 1996 and 2002 had splenic flexure mobilization only as required to achieve a tension-free anastomosis. Operative time, postoperative morbidity, pathologic findings, and recurrence rates were recorded. RESULTS: There were no clinicopathologic differences between those who had splenic flexure mobilization (n = 26) and those who did not (n = 74). Mean operative time in the splenic flexure mobilization group was longer, 167 (range, 130-200) minutes vs. 120 (range, 95-180) minutes in the nonmobilized group (P = 0.023). Mean length of specimen resected was longer in the splenic flexure mobilization group: 36 vs. 18 cm (P = 0.008). Anastomotic complications (4 percent), local recurrence (7 percent, median follow-up, 38 months), perioperative morbidity (32 percent) and mortality (2 percent), and survival did not differ between the two groups. CONCLUSIONS: Routine splenic flexure mobilization is not required for safe anterior resection in patients with rectal cancer. Avoiding splenic flexure mobilization results in shorter operative times and does not increase postoperative morbidity, anastomotic leakage, or local recurrence.

Adult↗

The significance of cutaneous spider naevi in children.

BACKGROUND: Cutaneous spider naevi are commonly considered to be a clinical sign of chronic liver disease. Little is known about their occurrence in children. AIM: To evaluate the occurrence of spider naevi in children with and without liver disease. METHODS: The presence of spider naevi was investigated in 460 children, 34 of whom had chronic liver disease. RESULTS: Of children without liver involvement, 38% had at least one spider naevus. The prevalence of spider naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more than five spiders present. Although eight of 10 children with cirrhosis had at least one spider naevus, only four of 34 children with chronic liver disease had five or more spiders present. Most spiders were on the hands and very few were >5 mm in size. CONCLUSIONS: Children with liver disease rarely have large numbers of spider naevi. Although the finding of five or more spider naevi is more common in liver disease, many normal children also have one or more of these lesions.

Adolescent↗

The indoor use of plastic sheeting pre-impregnated with insecticide for control of malaria vectors.

OBJECTIVE: To evaluate the efficacy of permethrin-treated plastic sheeting (ITPS) applied as a lining to the ceiling or walls of rooms against pyrethroid-susceptible and pyrethroid-resistant Anopheles gambiae. METHOD: Overnight tests were carried out in veranda-trap experimental huts in Vallée du Kou, where two molecular forms of A. gambiae, S and M, occur. The S form is mostly pyrethroid resistant due to the kdr mechanism, and the M form is mostly kdr susceptible. A variety of ITPS covered surfaces were tested, ranging from ceiling only to all walls plus ceiling covered. RESULTS: ITPS had a major effect on the mortality of mosquitoes, the proportion killed being dependent upon the surface area covered. Homozygotes for kdr resistance showed lower rates of mortality than did heterozygotes or homozygotes for susceptibility. Deterred entry of mosquitoes and inhibition of blood feeding were also correlated with surface area covered. The mode of action and efficacy of ITPS seems to bear closer resemblance to that induced by indoor residual spraying (IRS) than to that induced by insecticide-treated nets. CONCLUSIONS: ITPS might be conceived as being equivalent to long-lasting or permanent IRS but without some of the operational constraints normally associated with spraying. High coverage of ITPS could potentially have a mass population effect on mosquitoes and give rise to long-term community protection against malaria. A phase III trial is justified to assess the acceptability of ITPS and its efficacy against malaria.

Animals↗

Insecticide-treated bednets for the prevention of Plasmodium falciparum malaria in Cambodia: a cluster-randomized trial.

OBJECTIVES: To validate and quantify the impact of insecticide-treated bednets (ITN) on malaria morbidity and mortality in Cambodia. METHODS: A paired, cluster-randomized trial of ITN was conducted in Rattanakiri, North East Cambodia. Thirty-four villages with a total population of 10,726 were randomized to receive deltamethrin-impregnated bednets or to control (no net provision). Cross-sectional surveys measured Plasmodium falciparum prevalence at baseline and 10 months after ITN distribution. Village malaria volunteers in control and intervention villages treated dipstick-positive P. falciparum cases with artesunate and mefloquine. The resulting passive surveillance data were used as an estimate of the incidence of clinical P. falciparum infections. RESULTS: There was a protective efficacy of 28% in P. falciparum incidence (adjusted rate ratio 0.72, 95% CI 0.47-1.08) and 9% in P. falciparum prevalence (adjusted prevalence ratio 0.91, 95% CI 0.65-1.28) in ITN relative to control villages; however, neither of these estimates reached statistical significance. Individual-level analysis indicated a greater reduction in P. falciparum prevalence among under 5-year-olds (adjusted OR = 0.63, 95% CI 0.26-1.53) compared to older individuals (interaction P = 0.042). The protective efficacy of 35% (95% CI -28, 67%) with respect to clinical P. falciparum incidence in under 5-year-olds was more pronounced than the corresponding estimates for prevalence but was again not significant. CONCLUSIONS: Lack of statistical significance in the results is likely to be due to a lack of power. The analysis provides further evidence for ITN effectiveness in South East Asia, particularly among individuals under 5 years of age.

Adolescent↗

Comparison of the OptiMAL rapid antigen test with field microscopy for the detection of Plasmodium vivax and P. falciparum: considerations for the application of the rapid test in Afghanistan.

To establish the sensitivity and specificity of a batch of 'OptiMAL 48' rapid antigen tests procured by the World Health Organization in Afghanistan, a sample was tested, in parallel with routine, microscopical diagnosis, at basic health units (BHU) within Afghan refugee camps in Pakistan. The results of both methods of field diagnosis were compared with those of cross-checking microscopy at a reference laboratory, which were taken as the 'gold standard'. Out of 499 patients examined, 36% were diagnosed as malaria cases by field microscopy and 34% by the rapid test. For the OptiMAL 48 test, cross-checking of the corresponding smears at the reference laboratory gave a sensitivity of 79.3% and a specificity of 99.7% for Plasmodium falciparum and corresponding values of 86.1% and 98.7% for P. vivax infections. The performance of the field microscopy was better, with a sensitivity and specificity of 85.2% and 99.7% for P. falciparum, and 90.4% and 98.7% for P. vivax, respectively. These results show that the performance of OptiMAL 48 is adequate for acute- and post-emergency situations when the alternative is just clinical diagnosis. However, in the developing health system of Afghanistan, the main focus should be on the expansion of the existing network for microscopical diagnosis and quality control, to meet the needs of a stable situation. Rapid antigen tests are more suited to investigations of outbreaks in remote situations, where health services are deficient or absent.

Afghanistan↗

High altitude epidemic malaria in Bamian province, central Afghanistan.

We report an epidemic of Plasmodium falciparum malaria in the remote valley of Bamian (altitude 2250 m-2400 m) in the central highlands of Afghanistan. A team of malaria experts from the World Health Organization and HealthNet International carried out the investigation. A total of 215 peripheral blood smears were obtained and 63 cases of malaria (90.5% P. falciparum, the remainder P. vivax) were confirmed. The study revealed that areas vulnerable to malaria in Afghanistan are more widespread than previously recognized. The area had been malaria-free until recently, when the disease appears to have been introduced as a consequence of protracted conflict and resultant population movement, and transmitted locally during the short summer months. The outbreak led to severe morbidity and high mortality in a province having only a few poorly-provisioned health care facilities.

Adolescent↗

Resolution of P-glycoprotein and non-P-glycoprotein effects on drug permeability using intestinal tissues from mdr1a (-/-) mice.

1. Intestinal xenobiotic transporters are a significant barrier to the absorption of many orally administered drugs. P-glycoprotein (PGP) is the best known, but several others, including members of the multidrug resistance-associated protein (MRP) family, are also expressed. Definitive information on their precise effect on intestinal drug permeability is scarce due to a lack of specific inhibitors and the difficulty of studying non-PGP activity in the presence of high PGP expression. 2. We have investigated the in vitro use of intestinal tissues from PGP knockout (mdr1a (-/-)) mice as a tool for dissecting the mechanisms of intestinal drug efflux. The permeability characteristics of digoxin (DIG), paclitaxel (TAX) and etoposide (ETOP) were measured in ileum from mdr1a (-/-) and wild-type (FVB) mice mounted in Ussing chambers. 3. DIG and TAX exhibited marked efflux across FVB tissues (B-A : A-B apparent permeability (P(app)) ratio 10 and 17 respectively) which was absent in mdr1a (-/-) tissues, confirming that PGP is the sole route of intestinal efflux for these compounds. The A-B P(app) of both compounds was 3 - 5 fold higher in mdr1a (-/-) than in FVB. 4. Polarized transport of ETOP in FVB tissues was reduced but not abolished in mdr1a (-/-) tissues. Residual ETOP efflux in mdr1a (-/-) tissues was abolished by the MRP inhibitor MK571, indicating involvement of both PGP and MRP. 5. MK571 abolished calcein efflux in mdr1a (-/-) tissues, while quinidine had no parallel effect in FVB tissues, suggesting involvement of MRP but not PGP. 6. Tissues from mdr1a (-/-) mice provide a novel approach for investigating the influence of PGP ablation on intestinal permeability and for resolving PGP and non-PGP mechanisms that modulate drug permeability.

ATP Binding Cassette Transporter, Subfamily B↗

Comparison of three pyrethroid treatments of top-sheets for malaria control in emergencies: entomological and user acceptance studies in an Afghan refugee camp in Pakistan.

Insecticide-treated bedding materials (sheets and blankets) could be protective against vectors of malaria and leishmaniasis--especially in complex emergencies, epidemics and natural disasters where people are more likely to sleep in exposed situations. Comparison of cotton top-sheets impregnated with different pyrethroids (permethrin 500 mg/m2, deltamethrin 25 mg/m2 or alphacypermethrin 25 mg/m2) for effectiveness against mosquitoes (Diptera: Culicidae) was undertaken in a refugee camp in Pakistan. Predominant species encountered were Anopheles stephensi Liston, An. pulcherrimus Theobald, An. nigerrimus Giles, Culex quinquefasciatus Say, Cx. tritaeniorhynchus Giles and other culicine mosquitoes. All three pyrethroid treatments performed significantly better than the untreated sheets in deterrence and killing of mosquitoes. No significant differences were found between the three insecticides tested in terms of entomological effect. Washing of the treated sheets greatly reduced their effectiveness. In a user acceptance study conducted among 88 families (divided into four groups), six families complained of irritation of the skin and mucous membranes. Of these reports, one was from the placebo group (using untreated sheets) and the other five (5/22=23%) from families using deltamethrin-treated sheets. All families allocated to permethrin and alphacypermethrin groups declared an appreciation for the intervention and reported no side-effects. Ten of the placebo group disliked the intervention, citing no prevention of mosquito biting as the reason. Side-effects associated with deltamethrin indicate that alphacypermethrin and permethrin are more appropriate first choice insecticides for treatment of sheets and blankets.

Afghanistan↗

Insecticide-treated plastic tarpaulins for control of malaria vectors in refugee camps.

Spraying of canvas tents with residual pyrethroid insecticide is an established method of malaria vector control in tented refugee camps. In recent years, plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian shelter material for displaced populations in complex emergencies. Advances in technology enable polythene sheeting to be impregnated with pyrethroid during manufacture. The efficacy of such material against mosquitoes when erected as shelters under typical refugee camp conditions is unknown. Tests were undertaken with free-flying mosquitoes on entomological study platforms in an Afghan refugee camp to compare the insecticidal efficacy of plastic tarpaulin sprayed with deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin impregnated with deltamethrin (initially > or = 30 mg/m2) during manufacture, and a tent made from the factory impregnated tarpaulin material. Preliminary tests done in the laboratory with Anopheles stephensi Liston (Diptera: Culicidae) showed that 1-min exposure to factory-impregnated tarpaulins would give 100% mortality even after outdoor weathering in a temperate climate for 12 weeks. Outdoor platform tests with the erected materials (baited with human subjects) produced mosquito mortality rates between 86-100% for sprayed or factory-impregnated tarpaulins and tents (average approximately 40 anophelines and approximately 200 culicines/per platform/night), whereas control mortality (with untreated tarpaulin) was no more than 5%. Fewer than 20% of mosquitoes blood-fed on human subjects under either insecticide-treated or non-treated shelters. The tarpaulin shelter was a poor barrier to host-seeking mosquitoes and treatment with insecticide did not reduce the proportion blood-feeding. Even so, the deployment of insecticide-impregnated tarpaulins in refugee camps, if used by the majority of refugees, has the potential to control malaria by killing high proportions of mosquitoes and so reducing the average life expectancy of vectors (greatly reducing vectorial capacity), rather than by directly protecting refugees from mosquito bites. Mass coverage with deltamethrin-sprayed or impregnated tarpaulins or tents has strong potential for preventing malaria in displaced populations affected by conflict.

Afghanistan↗

Focally enhanced gastritis in children with Crohn's disease and ulcerative colitis.

OBJECTIVES: Focally enhanced gastritis (FEG) has been suggested as a specific diagnostic marker for patients with Crohn's disease. However, the utility of FEG for distinguishing Crohn's disease from ulcerative colitis is uncertain in adults, and the occurrence of this lesion in children has not been defined. The aim of this study was to evaluate the occurrence of FEG and other gastric histological abnormalities in children with inflammatory bowel disease (IBD) and to examine the utility of FEG in discriminating between ulcerative colitis and Crohn's disease. METHODS: This is a retrospective, case-controlled study of upper GI histopathological findings in children with IBD. Gastric histopathology was defined and graded according to the Updated Sydney System. RESULTS: FEG was present in 28 of 43 (65.1%) children with Crohn's disease and five of 24 (20.8%) children with ulcerative colitis, compared to three of 132 (2.3%) children without IBD or one of 39 (2.6%) children with Helicobacter pylori infection. There were no differences between those with and without FEG with regard to upper GI symptoms or previous anti-inflammatory drug ingestion (5-aminosalicylic acid compounds or steroids). All patients with H. pylori infection had chronic antral gastritis, but only one child with H. pylori had FEG. In addition, mild to moderate chronic gastritis was present in 15 of 43 (34.9%) children with Crohn's disease and in 12 of 24 (50%) patients with ulcerative colitis. CONCLUSIONS: The presence of FEG suggests underlying IBD. Although FEG is particularly common in children with Crohn's disease, it does not reliably differentiate between Crohn's disease and ulcerative colitis.

Case-Control Studies↗

Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001.

The authors present estimates of the economic costs to agriculture and industries affected by tourism of the outbreak of foot and mouth disease (FMD) in the United Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to about Pound Sterling3.1 billion. The majority of the costs to agriculture have been met by the Government through compensation for slaughter and disposal as well as clean-up costs. Nonetheless, agricultural producers will have suffered losses, estimated at Pound Sterling355 million, which represents about 20% of the estimated total income from farming in 2001. Based on data from surveys of tourism, businesses directly affected by tourist expenditure are estimated to have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2 billion) as a result of reduced numbers of people visiting the countryside. The industries which supply agriculture, the food industries and tourist-related businesses will also have suffered losses. However, the overall costs to the UK economy are substantially less than the sum of these components, as much of the expenditure by tourists was not lost, but merely displaced to other sectors of the economy. Overall, the net effect of FMD is estimated to have reduced the gross domestic product in the UK by less than 0.2% in 2001.

Agriculture↗

Control of malaria in Pakistan by applying deltamethrin insecticide to cattle: a community-randomised trial.

BACKGROUND: The standard method of malaria control in south Asia, indoor spraying of houses with residual insecticide, is becoming prohibitively expensive to implement and new approaches are needed. Since the region's vector mosquitoes feed predominantly on domestic animals and only secondarily on human beings, to apply insecticide to surfaces of cattle instead might be more costeffective. We aimed to investigate whether domestic livestock treated with deltamethrin (applied by a sponging method) would prove toxic to mosquitoes and therefore aid in malaria control. METHODS: Six Afghan refugee settlements in Pakistan were randomly assigned to one of two groups. In one group livestock were treated with deltamethrin during the malaria transmission seasons of 1995 and 1997, whereas in the other group livestock were treated during the 1996 season. Malaria was monitored by passive case detection at village clinics and by cross-sectional surveillance. Mosquitoes were also monitored. FINDINGS: According to clinic records the incidence of malaria caused by Plasmodium falciparum decreased by 56% (95% CI 14-78%) and P vivax by 31% (5-50%) in livestock-treated villages. Cross-sectional surveys showed comparable decreases in parasite prevalence. The density and life expectancy of Anopheles stephensi and A culicifacies populations were reduced in treated villages. The efficacy of livestock treatment was similar to that of indoor spraying but campaign costs were 80% less. When applied in a highly endemic settlement, the incidence of falciparum malaria decreased from 280 episodes per 1000 person-years to nine episodes per 1000 person-years. INTERPRETATIONS: Insecticide treatment of livestock is a cost-effective and promising alternative for south Asia and other regions where primary vectors are zoophilic.

Animals↗

A whole-body physiologically based pharmacokinetic model incorporating dispersion concepts: short and long time characteristics.

In whole-body physiologically based pharmacokinetic (PBPK) models, each tissue or organ is frequently portrayed as a single well-mixed compartment with distribution, perfusion rate limited. However, single-pass profiles from isolated organ studies are more adequately described by models which display an intermediate degree of mixing. One such model is the dispersion model, which successfully describes the outflow profiles from the liver and the perfused hindlimb of many compounds, under a variety of conditions. A salient parameter of this model is the dispersion number, a dimensionless term, which characterizes the relative axial spreading of compound on transit through the organ. We have developed a whole-body PBPK model wherein the distribution of drug on transit through each organ is described by the dispersion model with closed boundary conditions incorporated. The model equations were numerically solved using finite differencing methods, in particular, the method of lines. An integrating routine suitable for solving stiff sets of equations was used. Physiological parameters, blood flows, and tissue volumes, were taken from the literature, as were the tissue dispersion numbers, which characterize the mixing properties of each tissue; where none could be found, the value was set as that for liver. On solution, tissue, venous and arterial blood concentration-time profiles are generated. The profiles exhibited both short and long time characteristics. Oscillations were observed in the venous and arterial profiles over the first 10 min of simulation for the rat. On scale-up to human, the effects were seen over a 30 min period. Longer time effects of tissue distribution involve buildup of drug in the large tissues of distribution: skeletal muscle, skin, and adipose. The extent of distribution in the large tissues was somewhat dependent on the magnitude of the dispersion number, the lower the dispersion number, the greater the extent of distribution after an intravenous bolus dose. The model has a distinct advantage over the well-stirred organ whole-body PBPK model in its ability to describe both short and long time characteristics.

Animals↗

Limitations to carbon 13-labeled urea breath testing for Helicobacter pylori in infants.

We determined the validity of the carbon 13-labeled urea breath test in young children. We found that although the 13C-labeled urea breath test had a specificity greater than 90%, borderline or false positive results occurred more frequently in children younger than 2 years compared with older children. False positive results may be caused by oral-urease-producing organisms because direct intragastric administration of 13C urea reduced the excess delta 13CO2. Care is urged in interpreting one positive 13C-labeled urea breath test in children younger than 2 years.

Breath Tests↗

Malaria epidemiology and control in refugee camps and complex emergencies.

Owing to the breakdown of health systems, mass population displacements, and resettlement of vulnerable refugees in camps or locations prone to vector breeding, malaria is often a major health problem during war and the aftermath of war. During the initial acute phase of the emergency, before health services become properly established, mortality rates may rise to alarming levels. Establishing good case management and effective malaria prevention are important priorities for international agencies responsible for emergency health services. The operational strategies and control methods used in peacetime must be adapted to emergency conditions, and should be regularly re-assessed as social, political and epidemiological conditions evolve. During the last decade, research on malaria in refugee camps on the Pakistan-Afghanistan and Thailand-Burma borders has led to new methods and strategies for malaria prevention and case management, and these are now being taken up by international health agencies. This experience has shown that integration of research within control programmes is an efficient and dynamic mode of working that can lead to innovation and hopefully sustainable malaria control. United Nations' humanitarian and non-governmental agencies can play a significant part in resolving the outstanding research issues in malaria control.

Afghanistan↗

Tissue distribution and physiologically based pharmacokinetics of antisense phosphorothioate oligonucleotide ISIS 1082 in rat.

The aim of this study was to develop a whole body physiologically based model of the pharmacokinetics (PBPK) of the phosphorothioate oligonucleotide (PS-ODN) ISIS 1082 in vivo. Rats were administered an intravenous (i.v.) bolus dose of ISIS 1082 (10 mg/kg plus 3H tracer), and arterial blood and tissues were taken at specific times up to 72 hours. Radioactivity was measured in all samples. The parent compound was determined specifically in blood and tissues at 90 minutes and in liver and kidney also at 24 hours, using capillary gel electrophoresis (CGE). A whole body PBPK model was fitted to the combined blood and tissue radioactivity data using nonlinear regression analysis. CGE analysis indicated that the predominant species in plasma and all tissues is ISIS 1082, together with some n-1 and n-2 metabolites. Total radioactivity primarily reflects these species. The whole body model successfully described temporal events in all tissues. However, to adequately model the experimental data, all tissues had to be partitioned into vascular and extravascular spaces to accommodate the relatively slow distribution of ISIS 1082 out of blood because of a permeability rate limitation. ISIS 1082 distributes extensively into tissues, but the relative affinity varies enormously, being highest for kidney and liver and lowest for muscle and brain. A whole body PBPK model with a permeability rate limited tissue distribution was developed that adequately described events in both blood and tissue for an oligonucleotide. This model has the potential not only to characterize the events in individual tissues throughout the body for such compounds but also to scale across animal species, including human.

Adipose Tissue↗