Factors influencing initial implementation of an online community-based exercise intervention with adults living with HIV: a systems approach.

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists. Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis. Results: Thirty-three adults living with HIV enrolled in the study (n = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural, including weather and the COVID-19 virus; (ii) Societal, including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational, including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human, including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics. Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors.

EQ-5D-5L and SF-6D health utility index scores in patients with myasthenia gravis.

BACKGROUND AND PURPOSE: Health utilities are a preference-based method of valuing health states that are used in healthcare research, such as economic evaluations. There are limited health utility valuation data for patients with myasthenia gravis (MG). The aim of the study was to describe health utilities for patients with MG and different health states, using the EQ-5D-5L and SF-6D utility instruments, and to explore clinical and demographic determinants of utilities in this population. METHODS: Patients completed the EQ-5D-5L and SF-6D. In addition, patients were assessed with the Myasthenia Gravis Foundation of America classification, Myasthenia Gravis Impairment Index and MG-QOL15 as disease-specific measures, and the Neuro-QoL Fatigue scale. We calculated mean utilities for each Myasthenia Gravis Foundation of America severity class. We built regression models for the EQ-5D-5L and SF-6D to determine the clinical and demographic factors that determine patients' valuation of their health state. RESULTS: Among 254 patients, mean EQ-5D-5L health utilities were as follows: Remission, 0.94 ± 0.03; Minimal Manifestations, 0.92 ± 0.04; Class I, 0.89 ± 0.06; Class II, 0.78 ± 0.16; Class III, 0.58 ± 0.24 and Class IV, 0.61 ± 0.22. Mean SF-6D health utilities were as follows: Remission, 0.83 ± 0.07; Minimal Manifestations, 0.86 ± 0.14; Class I, 0.82 ± 0.14; Class II, 0.67 ± 0.12; Class III, 0.56 ± 0.11 and Class IV, 0.50 ± 0.10. The limb/axial scores were more highly correlated to health utilities than ocular or bulbar scores. CONCLUSIONS: We present estimates of health utilities for patients with MG that can be used in cost-utility and decision analyses. Limb/axial symptoms had a higher impact on health utilities than ocular or bulbar symptoms, which might reflect the impact of mobility on health valuation.

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.

Band-like calcification with simplified gyration and polymicrogyria: report of 10 new families and identification of five novel OCLN mutations.

Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) is an extremely rare autosomal recessive disorder with distinctive clinical and neuroimaging findings. To date, only 17 patients from 9 unrelated families with BLC-PMG have been reported worldwide. Herein, we describe a series of 13 new patients derived from 10 unrelated Egyptian families. Patients presented at early life with the classic phenotype including severe microcephaly, failure to acquire developmental skills, growth failure and the distinguished calcification patterns involving the cortex, thalami, basal ganglia and pons. Additional features not reported before included calcification of the cerebellum (eight patients: 61.5%) and imperforate anus and undescended testis in a single patient. Molecular studies of the OCLN gene (NM_001205254) identified six distinct candidate mutations. Interestingly, the deletion mutation of the transmembrane domain in exons 3 and 4 (c.51-?_730-?del, p.Lys18_Glu243) was found in five unrelated families (50%), suggesting a founder mutation in our population. On the other hand, five novel truncating mutations (c.809delA (p.K270Rfs*62), c.858_861delTTAT (p.I286Mfs*45), c.1037+5G>C, c.1169C>G (p.S390*) and c.1180delG (p.E394Sfs*91)) were detected, each in one family. To our knowledge, this is the largest series of patients with BLC-PMG. Cerebellum calcification is an additional relevant finding in our series, thus expanding the neuroradiological phenotype of this syndrome.

LOOP-MEDIATED ISOTHERMAL AMPLIFICATION (LAMP): SENSITIVE AND RAPID DETECTION OF SCHISTOSOMA HAEMATOBIUM DNA IN URINE SAMPLES OF EGYPTIAN SUSPECTED CASES.

Schistosomiasis haemalobium is a major endemic parasitic disease in many tropical regions including Egypt. Typical infection results in haematuria, dysuria, anaemia, genital as well as urinary tract lesions, with prospect of kidney damage in complicated cases. In addition, deposited eggs in the tissue, eventually leads to squamous cell carcinoma of urinary bladder in chronically infected individuals. Microscopic detection of excreted ova in urine samples remains the gold standard diagnostic method, in spite of its inherited low sensitivity, inconsistent egg excretion and unreliable results in chronic phase of the disease. Moreover due to pre-requisite for skilled personals and pricey equipment, PCR-based technologies are of limited use especially in low-income endemic countries. So emergence of loop-mediated isothermal DNA amplification (LAMP) seemed a promising technique. Our study evaluated application of LAMP technique in detection of S. haematobium DNA in 69 urine samples of suspected patients for urogenital schistosomiasis, versus conventional urine filtration followed by microscopy ova detection method. Specificity of LAMP was tested using other parasites DNA samples that showed no cross reactivity. Furthermore our results of the calculated diagnostic parameters for sensitivity and specificity for LAMP assay were 100%, with 95% CI (88.78%-100%), and 63.16%, with 95% CI (45.99%-78.19%) respectively, moreover Positive likelihood ratio (LR+) 2.7, and Negative likelihood ratio (LR-) 0.0, which display that LAMP technique is an up-to-date simple, sensitive, diagnostic important tool that could be employed in clinical diagnosis in poorly equipped facilities, as well as in surveillance of infectious diseases. As authors knowledge, this is the first national report evaluation of LAMP technique as a promising diagnostic tool for urogenital schistosomiasis.

Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

BACKGROUND: Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. RESULTS: Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. CONCLUSION: Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

Arthrocentesis followed by intra-articular autologous blood injection for the treatment of recurrent temporomandibular joint dislocation.

Temporomandibular joint (TMJ) dislocation is an excessive forward movement of the condyle beyond the articular eminence with complete separation of the articular surfaces and fixation in that position. This study was conducted to assess autologous blood injection to the TMJ for the treatment of chronic recurrent TMJ dislocation. Fifteen patients with bilateral chronic recurrent condylar dislocation were included in the study. Bilateral TMJ arthrocentesis was performed on each patient, followed by the injection of 2ml of autologous blood into the superior joint compartment and 1ml onto the outer surface of the joint capsule. Preoperative and postoperative assessment included a thorough history and physical examination to determine the maximal mouth opening, presence of pain and sounds, frequency of luxation, recurrence rate, and presence of facial nerve paralysis. Eighty percent of the subjects (12 patients) had a successful outcome with no further episodes of dislocation and required no further treatment at their 1-year follow-up, whereas three patients had recurrent dislocation as early as 2 weeks after treatment. Autologous blood injection is a safe, simple, and cost-effective treatment for chronic recurrent TMJ dislocation.

Evaluation of Cold and Thermal Fogging Spraying Methods for Mosquito Control.

The efficacy of three pyrethroid insecticides (lambda-cyhalothrin, deltamethrin, and cyphenothrin) in cold (CF) and thermal fogging (TF) applications against caged adults of Culex pipiens Linnaeus were evaluated under hot-dry conditions in Riyadh, Saudi Arabia. The efficacy of CF and TF at different distances from the release point (15, 30, 45, and 60 m) and height (1 and 2 m) was also investigated by evaluating adult mortality after 24 h of exposure. Our data indicated that TF was more efficacious than CF. While the distance from the spray path did not affect TF efficacy, CF showed decreased efficacy with the increase in distance from the spray path. Deltamethrin efficacy was significantly affected by both the application method and distance from the spray path, whereas lambda-cyhalothrin was only affected by the spray method.

Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?

UNLABELLED: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted. INTRODUCTION: Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist. METHODS: We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day). RESULTS: Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses. CONCLUSIONS: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.

Preferences for surveillance strategies for women treated for high-grade precancerous cervical lesions.

OBJECTIVES: Data are lacking on how women view alternative approaches to surveillance for cervical cancer after treatment of high-grade cervical intraepithelial neoplasia. We measured and compared patient preferences (utilities) for scenarios with varying surveillance strategies and outcomes to inform guidelines and cost-effectiveness analyses of post-treatment surveillance options. METHODS: English- or Spanish-speaking women who had received an abnormal Pap test result within the past 2 years were recruited from general gynecology and colposcopy clinics and newspaper and online advertisements in 2007 and 2008. Participation consisted of one face-to-face interview, during which utilities for 11 different surveillance scenarios and their associated outcomes were elicited using the time tradeoff metric. A sociodemographic questionnaire also was administered. RESULTS: 65 women agreed to participate and successfully completed the preference elicitation exercises. Mean utilities ranged from 0.989 (undergoing only a Pap test, receiving normal results) to 0.666 (invasive cervical cancer treated with radical hysterectomy or radiation and chemotherapy). Undergoing both Pap and HPV tests and receiving normal/negative results had a lower mean utility (0.953) then undergoing only a Pap test and receiving normal results (0.989). Having both tests and receiving normal Pap but positive HPV results was assigned an even lower mean utility (0.909). 15.9% of the respondents gave higher utility scores to the Pap plus HPV testing scenario (with normal/negative results) than to the "Pap test alone" scenario (with normal results), while 17.5% gave the Pap test alone scenario a higher utility score. CONCLUSIONS: Preferences for outcomes ending with normal results but involving alternative surveillance processes differ substantially. The observed differences in utilities have important implications for clinical guidelines and cost-effectiveness analyses.

Cost-effectiveness of voluntary HIV screening in Russia.

Russia has one of the world's fastest growing HIV epidemics, and HIV screening has been widespread. Whether such screening is an effective use of resources is unclear. We used epidemiologic and economic data from Russia to develop a Markov model to estimate costs, quality of life and survival associated with a voluntary HIV screening programme compared with no screening in Russia. We measured discounted lifetime health-care costs and quality-adjusted life years (QALYs) gained. We varied our inputs in sensitivity analysis. Early identification of HIV through screening provided a substantial benefit to persons with HIV, increasing life expectancy by 2.1 years and 1.7 QALYs. At a base-case prevalence of 1.2%, once-per-lifetime screening cost $13,396 per QALY gained, exclusive of benefit from reduced transmission. Cost-effectiveness of screening remained favourable until prevalence dropped below 0.04%. When HIV-transmission-related costs and benefits were included, once-per-lifetime screening cost $6910 per QALY gained and screening every two years cost $27,696 per QALY gained. An important determinant of the cost-effectiveness of screening was effectiveness of counselling about risk reduction. Early identification of HIV infection through screening in Russia is effective and cost-effective in all but the lowest prevalence groups.

Current assessment of risk-benefit by regulators: is it time to introduce decision analyses?

Regulatory risk-benefit assessments may overweight small but serious risks relative to benefits. Using terfenadine and torsade de pointes as an exemplar, we illustrate how a different decision may result when outcomes are assessed using quality-adjusted life-years within a decision-analytical framework. The adoption of common measures of health outcome and the use of decision analyses, which will allow uncertainty to be characterized and evidence to be compiled from disparate sources, may inform complex risk-benefit decisions and should be used in conjunction with qualitative assessments.

Adverse quality of life consequences of antiretroviral medications.

To identify the effects of antiretroviral therapy on quality of life, we performed a qualitative content analysis of the Medical Outcomes Study-Human Immunodeficiency Virus (MOS-HIV) Health Survey. We used focus groups to elicit views about antiretroviral effects on quality of life from a purposive sample of treatment-experienced participants. Data were analysed using a grounded theory approach. We appraised the content of the MOS-HIV against the themes identified from our analysis. Participants also completed the MOS-HIV survey and were asked whether the survey captured all important medication-related aspects of quality of life. Participants (n=38) viewed the use of antiretrovirals as a trade-off between poorer quality of life and being alive. The net effect was increased longevity but without hope and future. Features of quality of life included the downstream consequences of side effects and toxicities, tensions with health care providers and loss of independent decision-making, dilemmas regarding drugs and career, burdens of medication-taking responsibilities, and the stress of living life under a pretense and hiding an HIV diagnosis. The MOS-HIV missed or under-emphasised these features. Quality of life concerns of people living with HIV, particularly those related to medication use, are not well captured by the MOS-HIV. A broad concept of quality of life is needed to encompass all dimensions important to people living with HIV.

Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS.

BACKGROUND: Adherence to prescribed regimens is required to derive maximal benefit from many highly active antiretroviral therapy (HAART) regimens in people living with HIV/AIDS. OBJECTIVES: To conduct a systematic review of the research literature on the effectiveness of patient support and education to improve adherence to HAART. SEARCH STRATEGY: A systematic search of electronic databases was performed from January 1996 to May 2005. SELECTION CRITERIA: Randomized controlled trials examining the effectiveness of patient support and education to improve adherence to HAART were considered for inclusion. Only those studies that measured adherence at a minimum of six weeks were included. DATA COLLECTION AND ANALYSIS: Study selection, quality assessments and data abstraction were performed independently by two reviewers. MAIN RESULTS: Nineteen studies involving a total of 2,159 participants met criteria for inclusion. It was not possible to conduct a meta-analysis due to study heterogeneity with respect to populations, interventions, comparison groups, outcomes, and length of follow-up. Sample sizes ranged from 22 to 367. The populations studied ranged from general HIV-positive populations to studies focusing exclusively on children, women, Latinos, or adults with a history of alcohol dependence, to studies focusing almost exclusively on men. Study interventions included cognitive behavioral therapy, motivational interviewing, medication management strategies, and interventions indirectly targeting adherence, such as programs directed to reduce risky sexual behaviours. Ten studies demonstrated a beneficial effect of the intervention on adherence. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We were unable to determine whether effective adherence interventions were associated with improved virological or immunological outcomes. Most studies had several methodological shortcomings leaving them vulnerable to potential biases. AUTHORS' CONCLUSIONS: We found evidence to support the effectiveness of patient support and education interventions intended to improve adherence to antiretroviral therapy. Interventions targeting practical medication management skills, those interventions administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. There is a need for standardization and increased methodological rigour in the conduct of adherence trials.

The impact of home nocturnal hemodialysis on end-stage renal disease therapies: a decision analysis.

Home nocturnal hemodialysis (HNHD) is cost-effective relative to in-center hemodialysis (IHD) in short-run analyses. The effect in long-run analyses, when technique failures, declining benefits, delayed training, transplantation and death are considered, is unknown. We used decision analysis techniques to examine the relative cost-effectiveness of HNHD and IHD, projecting future costs and health effects over a lifetime with end-stage renal disease. We developed a Markov state-transition model comparing two strategies: only IHD or starting on IHD and subsequently transferring to HNHD. The model incorporates transplantation. In the base case, half the population was eligible for transplantation, with (1/3) of grafts from live donors. The time to transplant was 0.75 years for live and 5 years for deceased donor transplants. The delay before initiation of HNHD was 5 years. Costs and outcomes were discounted at 3% per annum. Model parameters were derived from a literature review. We also conducted one-way sensitivity analyses and Monte Carlo simulations. The HNHD strategy was associated with a quality-adjusted survival estimate of 5.79 quality-adjusted life years (QALYs), with lifetime costs of $538 094. The values for IHD were 5.31 QALYs and $543 602, respectively. Thus, HNHD is cost saving while improving quality of life. The incremental cost-utility ratio was consistently less than $50 000 per QALY in sensitivity and Monte Carlo analyses. Important determinants of cost-effectiveness were transplantation time and whether benefits declined over time. Our model suggests that HNHD improves quality-adjusted survival over IHD at an economically attractive cost-effectiveness ratio.

Maternal and Childhood Mortality in the Nuba Mountains; Sudan: A Pilot Study

The aim of the pilot study was to establish baseline levels for maternal mortality ratio (MMR) and childhood mortality rates measured prospectively in the Nuba Mountains; an under-privileged area of the Sudan; and compare them to pervious national retrospective surveys. A communal vital registration system was established as a pilot study in a defined community in the Nuba Mountains area; Sudan; including two strata; Dilling and Um Ruwaba Provinces. Live events were registered for 6-months. 1;913 live births; 268 childhood (0-4 years) deaths and 13 maternal deaths were registered during the period of study; July 2001-June 2002. Childhood mortality rates per 1;000 live births were: Infant (IMR) 85; child (CMR) 55; and under-five (U5MR) 140. There was no significant difference between Dilling stratum and Um Ruwaba stratum in IMR (x/2 = 1.56; P 0.05). CMR and U5MR were significantly higher in Um Ruwaba stratum (x/2 = 6.619; P 0.05 and x/2 0.05). All rates were much higher than those quoted for the country by previous retrospective survey estimates. Prospectively determined childhood and maternal mortality rates using a communal vital registration system appear to be higher but more realistic for a disadvantaged area compared to retrospective estimates. The wide discrepancy indicates the need for debating the limitations and relevance of the latter

Cytotoxic effects of two antimolting insecticides in mammalian CHO-K1 cells.

Cytotoxicity of two insect growth regulators, diflubenzuron, a benzoylphenylurea derivative that inhibits the synthesis of new chitin in target organisms, and pyriproxyfen, an insect juvenile hormone analogue, were tested on CHO-K1 cultures, using the neutral red incorporation assay. Both compounds displayed cytotoxic effects that rise with time exposure. The presence of either fetal calf serum or bovine serum albumin diminished significantly the cytotoxicity of both compounds, thus pointing to a strong protein binding. In addition, extensive metabolization with rat liver submitochondrial fraction gave rise to metabolites less toxic than the parent compounds, implying the relative safety of both diflubenzuron and pyriproxyfen in mammals.

Changes in glutathione-redox balance induced by hexachlorocyclohexane and lindane in CHO-K1 cells.

1. The basal cytotoxic effect of the organochlorine pesticides hexachlorocyclohexane and lindane on CHO-K1 cultures was assessed at fractions of their lethal doses as determined by the neutral red incorporation (NRI) assay (NRI(6.25), NRI(12.5) and NRI(25)). The sulphur-redox cycle enzymes glutathione peroxidase, glutathione reductase and glutathione S-transferase, and total and oxidized glutathione were evaluated at several points during the standard growth curve of the cultures. 2. After incubation with each compound for 24 h, both glutathione peroxidase and reductase showed a substantial increase at the lowest exposure doses (NRI(6.25))--more significantly for lindane than for 1,2,3,4,5,6-hexachlorocyclohexane (HCH)--and dropped at higher doses of both compounds. The reduced and oxidized glutathione content was greatly diminished at the lower exposures, whereas the total glutathione content was higher at NRI(12.5) values. 3. Changes in cell membrane integrity were assessed for a wide range of pesticide concentrations with the lactate dehydrogenase release assay and lipid peroxidation. Membrane leakage and peroxide production were significantly enhanced at concentrations of HCH 50 microg ml(-1), although this effect was not significant at lindane concentrations < 200 microg ml(-1). 4. Lipid peroxidation increased with exposure to HCH at concentrations as low as NRI(6.25), whereas in the case of lindane, this increase was only significant at doses of NRI(25) and above.