A feasibility study of perioperative vitamin D supplementation in patients undergoing colorectal cancer resection.

Background: Vitamin D supplementation improves colorectal cancer (CRC) survival outcomes in randomized trials. The aim of this study was to test the feasibility, safety and efficacy of vitamin D supplementation in the pre- and perioperative period in patients undergoing CRC surgery. Methods: Patients were given 3200IU oral cholecalciferol (D3) per day perioperatively. Serial serum 25-hydroxyvitamin (25OHD) was measured by liquid chromatography tandem mass spectrometry and compared to untreated CRC controls. 25OHD and C-reactive protein (CRP) levels were compared using adjusted generalized linear mixed-effects models. Results: A total of 122 patients underwent serial perioperative sampling, including 41 patients given high-dose perioperative supplementation. Supplementation was well-tolerated with no adverse or serious adverse events related to supplementation reported. Pre-operative supplementation increased 25OHD levels on the day of surgery (103.9 vs. 42.5 nmol/l, P = 8.2E-12). Supplementation increased 25OHD levels at all post-operative timepoints (P < 0.001) and attenuated the post-operative drop in 25OHD (46 vs. 24% drop, P = 3.0E-4). Rate of vitamin D peri-operative insufficiency was significantly less in those on supplementation (e.g., day 3-5, 14 vs. 84%, P = 1.41E-08), with multivariate modeling across all timepoints indicating a ∼59 nmol/l higher 25OHD compared to control patients (P = 3.7E-21). Post-operative CRP was lower in patients taking supplementation (e.g., day 3-5 timepoint; 129 vs. 81 mg/l, P = 0.04). Conclusion: High dose pre-operative vitamin D supplementation is associated with higher perioperative 25OHD levels, lower rates of vitamin D insufficiency and reduced early post-operative CRP. Alongside published evidence for a beneficial effect of vitamin D on CRC survival outcomes, these novel findings provide strong rationale for early initiation of vitamin D supplementation after a diagnosis of CRC.

Double faecal immunochemical testing in patients with symptoms suspicious of colorectal cancer.

BACKGROUND: Faecal immunochemical test (FIT)-directed pathways based on a single test have been implemented for symptomatic patients. However, with a single test, the sensitivity is 87 per cent at 10 µg haemoglobin (Hb) per g faeces. This aims of this study were to define the diagnostic performance of a single FIT, compared with double FIT in symptomatic populations. METHODS: Two sequential prospective patient cohorts referred with symptoms from primary care were studied. Patients in cohort 1 were sent a single FIT, and those in cohort 2 received two tests in succession before investigation. All patients were investigated, regardless of having a positive or negative test (threshold 10 µg Hb per g). RESULTS: In cohort 1, 2260 patients completed one FIT and investigation. The sensitivity of single FIT was 84.1 (95 per cent c.i. 73.3 to 91.8) per cent for colorectal cancer and 67.4 (61.0 to 73.4) per cent for significant bowel pathology. In cohort 2, 3426 patients completed at least one FIT, and 2637 completed both FITs and investigation. The sensitivity of double FIT was 96.6 (90.4 to 99.3) per cent for colorectal cancer and 83.0 (77.4 to 87.8) per cent for significant bowel pathology. The second FIT resulted in a 50.0 per cent reduction in cancers missed by the first FIT, and 30.0 per cent for significant bowel pathology. Correlation between faecal Hb level was only modest (rs = 0.58), and 16.8 per cent of double tests were discordant, 11.4 per cent in patients with colorectal cancer and 18.3 per cent in those with significant bowel pathology. CONCLUSION: FIT in patients with high-risk symptoms twice in succession reduces missed significant colorectal pathology and has an acceptable workload impact.

Radiology of Castleman disease: the pivotal role of imaging in diagnosis, staging, and response assessment of this rare entity.

Castleman Disease (CD) is a rare entity that typically presents as an enhancing nodal mass in the mediastinum or head and neck region on computed tomography (CT). It may manifest as unicentric or multicentric regions of lymph node enlargement. A key clinical issue in the context of CD is delayed diagnosis, which contributes adversely to patient outcome, given that accurate diagnosis facilitates earlier treatment of this curable disease. This article will address relevant imaging aspects, with reference to typical and atypical imaging features of CD, illustrated using examples from our specialist centre; the imaging journey for patients with CD; and will provide practical pointers to radiologists in differentiating CD from other benign and malignant causes of enhancing lymphadenopathy, including lymphoma and neoplastic adenopathy. We will also review current classification tools and staging challenges with reference to World Health Organization guidelines, International Working Group guidelines as well as the Lugano classification. Finally, we will discuss the potential role of additional imaging techniques in CD, highlighting novel imaging methods and expanded utilities from our specialist centre.

Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects.

BACKGROUND: The risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. METHODS: Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). RESULTS: Six hundred twenty-nine genes were associated with 25-OHD level (P < 0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P < 1.0E-07; downregulated gene-set P < 2.6E-05) and corresponding GO terms (P = 2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P < 0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI 0.66-1.00]) and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI 0.77-0.89]; PPP1CC AUC=0.91 [95%CI 0.86-0.95]). CONCLUSIONS: Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects, and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumour transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.

Risk of missing colorectal cancer with a COVID-adapted diagnostic pathway using quantitative faecal immunochemical testing.

BACKGROUND: COVID-19 has brought an unprecedented challenge to healthcare services. The authors' COVID-adapted pathway for suspected bowel cancer combines two quantitative faecal immunochemical tests (qFITs) with a standard CT scan with oral preparation (CT mini-prep). The aim of this study was to estimate the degree of risk mitigation and residual risk of undiagnosed colorectal cancer. METHOD: Decision-tree models were developed using a combination of data from the COVID-adapted pathway (April-May 2020), a local audit of qFIT for symptomatic patients performed since 2018, relevant data (prevalence of colorectal cancer and sensitivity and specificity of diagnostic tools) obtained from literature and a local cancer data set, and expert opinion for any missing data. The considered diagnostic scenarios included: single qFIT; two qFITs; single qFIT and CT mini-prep; two qFITs and CT mini-prep (enriched pathway). These were compared to the standard diagnostic pathway (colonoscopy or CT virtual colonoscopy (CTVC)). RESULTS: The COVID-adapted pathway included 422 patients, whereas the audit of qFIT included more than 5000 patients. The risk of missing a colorectal cancer, if present, was estimated as high as 20.2 per cent with use of a single qFIT as a triage test. Using both a second qFIT and a CT mini-prep as add-on tests reduced the risk of missed cancer to 6.49 per cent. The trade-off was an increased rate of colonoscopy or CTVC, from 287 for a single qFIT to 418 for the double qFIT and CT mini-prep combination, per 1000 patients. CONCLUSION: Triage using qFIT alone could lead to a high rate of missed cancers. This may be reduced using CT mini-prep as an add-on test for triage to colonoscopy or CTVC.

Development, Characterization, and Evaluation of SLN-Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery.

BACKGROUND: Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. RESULTS: TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat's rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. CONCLUSION: It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.

Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.

Association between pain catastrophising and musculoskeletal disorders is modified by past injuries in Malaysian military recruits.

OBJECTIVES: Pain catastrophising is defined as exaggerated negative thoughts, which can occur during an actual or anticipated painful experience, such as musculoskeletal injuries (MSI) or disorders (MSD). The aims of this study are to examine the association between pain catastrophising and MSI and MSD in Malaysian Army male recruits, and evaluate the effects of past injury. METHODS: A cohort of 611 male Malaysian Army recruits were recruited and followed up at 3 and 6 months. Pain catastrophising, MSD, sociodemographic and work factors were measured using a self-administered questionnaire, and MSI incidence was retrieved from the medical records. Multivariable fixed effects regression was used to model the cumulative incidence of MSD and MSI. RESULTS: Approximately 12% of the recruits were diagnosed with incident MSI and 80% reported incident MSD. Higher pain catastrophising at baseline was associated with higher 6 month MSD risk (adjusted OR (aOR) 1.6 per 1 SD increase of Pain Catastrophising Scale (PCS) scores; 95% CI 1.2 to 2.0), and longitudinally associated with MSD incidence (aOR 1.2, 95% CI 1.1 to 1.4). Pain catastrophising was not associated with MSI incidence (aOR 1.0, 95% CI 0.8 to 1.3). The association between pain catastrophising and self-reported MSD was stronger among recruits with self-reported past injury (p for interaction <0.001). CONCLUSIONS: Pain catastrophising was able to predict symptomatic MSD, and not physician-diagnosed MSI, and these findings are directly related to individual health beliefs. Pain catastrophising has a greater influence on how military recruits perceived their musculoskeletal conditions during training, and efforts to reduce pain catastrophising may be beneficial.

Cultural adaptation and psychometric assessment of Pain Catastrophizing Scale among young healthy Malay-speaking adults in military settings.

PURPOSE: The Pain Catastrophizing Scale (PCS) is designed to assess negative thoughts in response to pain. It is composed of three domains: helplessness, rumination, and magnification. We report on the translation, adaptation, and validation of scores on a Malay-speaking version of the PCS, the PCS-MY. METHOD: Guidelines for the process of cross-cultural adaptations of assessment measures were implemented. A sample of 303 young military recruits participated in the study. Factor structure, reliability, and validity of scores on the PCS-MY were examined. Convergent validity was investigated with the Positive and Negative Affect Scale, Short-form 12 version 2, and Ryff's Psychological Well-being Scale. RESULTS: Most participants were men, ranging in age from 19 to 26. The reliability of the PCS-MY scores was adequate (α = 0.90; mean inter-item correlation = 0.43). Confirmatory factor analysis showed that a modified version of the PCS-MY provided best fit estimates to the sample data. The PCS-MY total score was negatively correlated with mental well-being and positively correlated with negative affect (all ps < 0.001). CONCLUSION: The PCS-MY was demonstrated to have adequate reliability and validity estimates in the study sample.

Aspirin-induced nuclear translocation of NFkappaB and apoptosis in colorectal cancer is independent of p53 status and DNA mismatch repair proficiency.

Substantial evidence indicates nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC). However, the molecular basis for this anti-tumour activity has not been fully elucidated. We previously reported that aspirin induces signal-specific IkappaBalpha degradation followed by NFkappaB nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. We have also reported the relative specificity of this aspirin-induced NFkappaB-dependent apoptotic effect for CRC cells, in comparison to other cancer cell types. It is now important to establish whether there is heterogeneity within CRC, with respect to the effects of aspirin on the NFkappaB pathway and apoptosis. p53 signalling and DNA mismatch repair (MMR) are known to be deranged in CRC and have been reported as potential molecular targets for the anti-tumour activity of NSAIDs. Furthermore, both p53 and MMR dysfunction have been shown to confer resistance to chemotherapeutic agents. Here, we set out to determine the p53 and hMLH1 dependency of the effects of aspirin on NFkappaB signalling and apoptosis in CRC. We specifically compared the effects of aspirin treatment on cell viability, apoptosis and NFkappaB signalling in an HCT-116 CRC cell line with the p53 gene homozygously disrupted (HCT-116(p53-/-)) and an HCT-116 cell line rendered MMR proficient by chromosomal transfer (HCT-116(+ch3)), to the parental HCT-116 CRC cell line. We found that aspirin treatment induced apoptosis following IkappaBalpha degradation, NFkappaB nuclear translocation and repression of NFkappaB-driven transcription, irrespective of p53 and DNA MMR status. These findings are relevant for design of both novel chemopreventative agents and chemoprevention trials in CRC.

Evidence for colorectal cancer cell specificity of aspirin effects on NF kappa B signalling and apoptosis.

Epidemiological evidence indicates that non-steroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC) to a greater degree than other non-gastrointestinal cancers, but the molecular basis for this difference is unknown. We previously reported that aspirin induces signal-specific I kappa B alpha degradation followed by NF kappa B nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. Here, we explored the hypothesis that cell-type specific effects on NF kappa B signalling are responsible for the observed differences in protection by aspirin against CRC compared to breast and gynaecological cancers. We also assessed whether COX-2 expression, mutation status of adenomatous polyposis coli (APC), beta-catenin, p53, or DNA mismatch repair (MMR) genes in CRC lines influenced aspirin-induced effects. We found that aspirin induced concentration-dependent I kappa B alpha degradation, NF kappa B nuclear translocation and apoptosis in all CRC lines studied. However, there was no such effect on the other cancer cell types, indicating a considerable degree of cell-type specificity. The lack of effect on NF kappa B signalling, paralleled by absence of an apoptotic response to aspirin in non-CRC lines, strongly suggests a molecular rationale for the particular protective effect of NSAIDs against CRC. Effects on NF kappa B and apoptosis were observed irrespective of COX-2 expression, or mutation status in APC, beta-catenin, p53 and DNA MMR genes, underscoring the generality of the aspirin effect on NF kappa B in CRC cells. These findings raise the possibility of cell-type specific targets for the development of novel chemopreventive agents.

[Current malaria situation in the Republic of Kazakhstan]. / Sovremennaia situatsiia po maliarii v Respublike Kazakhstan.

The Republic of Kazakhstan is situated in the northern hemisphere on the boundary of two continents--Europe and Asia--at a longitude of 45 degrees E--87 degrees E and a latitude of 40 degrees N--55 degrees N. The total area of the republic is 2,724,900 square kilometers. Kazakhstan shares a border with the Russian Federation to the north-west, north and east: the border between the two countries is almost 6500 km long. To the south, Kazakhstan shares a border with the Central Asian states of Turkmenistan (380 km), Uzbekistan (2300 km) and Kyrgystan (980 km). To the south-east, it shares a border with China (1460 km): to the west is the Caspian Sea (600 km). Thus, the total length of Kazakhstan's external borders is 12,000 km. Because of the geographical, natural and climatic features prevailing throughout most of the Republic, there is a potential danger that local transmission of malaria may begin again if the disease is imported from abroad. The areas most at risk are the Panfilov and Uigur raions of Almaty oblast, which share a border with malaria-endemic regions of China, and the Saryagash and Makhtaral' raions of South Kazakhstan oblast along the border with Uzbekistan. The Government of the Republic of Kazakhstan places particular emphasis on malaria prevention and control, taking into account the historical data about the prevalence of malaria from the late 1920s to the early 1940s, amounting to hundreds of thousands of cases every year. Government Decree No. 840 entitled "Urgent Measures to Protect the Population from Blood-Sucking Insects and Ticks Dangerous to Humans", which lays down measures for the control of malarial mosquitoes in the areas most susceptible to malaria resurgence, was adopted in 1996. The Ministry of Health of the Republic of Kazakhstan issued instructions in 1998 and 1999 which were designed to motivate all health facilities in the field of malaria prevention and control. At present, as part of the directives developed by the Republican Health Epidemiology Posts, work is being done on the planning of malaria control measures in Kazakhstan for the period 2001-2003. In 1994 a programme of epidemiological malaria surveillance was introduced, which has enabled us to improve our monitoring of the epidemiological situation of malaria. The number of cases of imported malaria has declined: in 1997, there were 102 cases, in 1998-87 and in 1999-52. There have been occasional local cases in some years, and in 1998 there were four local cases in the south and north-west of the country: two cases in Almaty oblast, one case in Zhambyl oblast and one in West Kazakhstan oblast (see Fig. 1). Most malaria infections are imported from Tajikistan and Azerbaijan, with occasional cases from Pakistan, India, Turkey and Afghanistan. Analysis of the occupational status of patients shows that around 45% are military personnel who have served on the Tajik-Afghan border. The others are refugees, merchants, unemployed people or students. The overall aetiological structure of malaria cases is dominated by P. vivax malaria. For example, in 1999, there were 48 cases of P. vivax malaria (90.5% of the total), one case of tropical malaria (1.9%), two cases of quartan malaria (3.8%) and two cases of P. vivax + P. malariae (3.8%). In order to prevent indigenous malaria occurring within the country, a system of malaria screening has been set up; screening is carried out every year on groups who have visited neighbouring or more distant malaria-endemic countries and for patients with a persistent fever who are suspected of suffering from malaria. The area of water throughout the country within communities or within a 3-5 km radius of them which is susceptible to colonization by the Anopheles mosquito amounts to over 5000 hectares, according to the certification system in force. In addition, approximately 70,000 hectares in three oblasts used for rice cultivation also provide a habitat for Anopheles. The main malaria vector, An. messeae, is found throughout the country: in a few areas An. hyrcanus and An. claviger are found and, in the south, An. pulcherrimus. Data from recent years show the presence of An. superpictus, An. plumbeus and An. algeriensis. In 1999, from data collected during systematic observations of the phenology and seasonal variations in the number of Anopheles at 114 observation posts, the average seasonal numerical indicators for the mosquito imago reached a maximum of between 21 and 46.5 adult mosquitoes per cattle shed, up to 2.7-3.3 adult mosquitoes per residential building and 30-67.3 larvae per square metre of surface water. According to the results of large scale trapping programmes (486 communities were screened in 1999), the maximum value of the numerical indicator was 16.8-74.1 adult mosquitoes per cattle shed and 4.1-3.8 adult mosquitoes per residential building. In 1999, compared with 1998, the number of malarial mosquitoes detected throughout the country declined encouragingly, or stayed at the same level, which is one of the factors responsible for the country's favourable epidemiological situation with regard to malaria. According to data going back many years, there has been a significant increase in the number of mosquitoes at some observation posts in Almaty, East Kazakhstan and Kyzlorda oblasts. There is a tendency everywhere for the numbers of imagos detected in residential buildings to increase, which presents a definite epidemiological risk that indigenous malaria will re-emerge if the disease is imported into Kazakhstan from countries which suffer from it. If we consider the species of mosquito present in the country and the temperature factor (the number of days in the year when the average daily temperature is over 16 degrees C), the country can be divided, on the basis of incomplete 1999 data, into zones at very high risk of re-emergence of malaria (Almaty, Zhambyl and South Kazakhstan oblasts), high risk (Karaganda oblasts and Almaty city), medium risk (Aktyubinsk and Akmolinsk oblasts), and low risk (Kostanay oblast). The malaria risk of the other oblasts has been calculated using data from earlier years (map attached) [Translator's Note: map missing]. Preventive malaria control measures in Kazakhstan are divided into three categories to suit three different groups of communities. One hundred and seventy-nine communities have been allocated to the first group, at high risk of malaria resurgence; 1377 communities to the second group, at medium risk; and the remainder to the third group, at little or no risk of malaria resurgence. The following factors were used to categorize communities according to the risk that malaria might become reestablished if the disease should be imported from elsewhere: species of malarial mosquito present; changes in mosquito numbers and in the area of water susceptible to population by Anopheles; temperature conditions and, consequently, the length of the malaria transmission season and the season of effective susceptibility of the mosquito to infection; population migration; quality of laboratory testing for the diagnosis of malaria. Measures aimed at the destruction of mosquitoes are intended to reduce the numbers of Anopheles in the communities most at risk of malaria resurgence, i.e. those in group 1 above and the actual foci of malaria infection. Because of the economic crisis and financial difficulties, fewer areas have been treated in recent years. In 1999, 1387 hectares of water and 450,000 square metres of buildings were treated (see Fig. 2). Measures to control biting flies in health establishments, recreation areas, etc. Certainly also help to protect people from malarial mosquitoes. In 1999, 12,501 hectares of water and land were treated from the ground or the air (see Fig. 3). In the present situation, the main reasons for the difficulties affecting the malaria control and prevention campaign are as follows. Staff numbers in the Republic's parasitology service have been unjustifiably reduced. For example, the number of entomologists and entomology assistants employed is 58% and 48%, respectively, of the number laid down in Ministry of Health directives. At the health epidemiology posts, the number of disinfectors has been reduced to a minimum, and practically all engineer/water engineer posts have been abolished. The country does not possess the necessary education base for initial training or continuing education of staff for the parasitology service. The lack of basic scientific information about the problems of malaria control and prevention and parasitology in general. There is no research to test or introduce the most effective, safe and low-cost malaria control products and insecticides. The methodological literature required to use certain modern insecticides is not available. Entomologists are not provided with specialist insect control equipment. Entomological surveys are left incomplete because of shortages of transport and fuel at the health epidemiology posts. Because of the economic crisis and the high cost of the radical water engineering measures necessary to combat malaria, these measures cannot be implemented on the scale required. The equipment and materials stocks of the parasitology laboratories are highly inadequate: there is a lack of modern laboratory equipment, as well as a lack of opportunities for high-level professional training for staff. The exchange of information between the CIS countries is unsatisfactory, and there is no common information space: nor is there any systematic data available from other foreign countries. In the period 2000-2003, Kazakhstan plans to carry out malaria control activities (mosquito destruction) over an area of 2000 hectares of water and 1.5 million square metres of buildings.

Interocclusal records--a review of three common recording materials.

In restorative and prosthetic dental treatment, casts which duplicate the patient's dentition are frequently mounted in an articulator which simulates jaw movements. In order to relate the mandibular cast to the maxillary cast, records are made in the mouth utilising suitable materials. Three common recording materials will be discussed.