Efficacy of Mepliex® Ag Versus Xeroform® As A Split-Thickness Skin Graft Donor Site Dressing: Bad Habits Die Hard.

Autografting with split-thickness skin grafts (STSG) remains an essential procedure in burn and reconstructive surgery. The process of harvesting STSG, however, leaves behind a donor site, an exposed area of partial-thickness dermis left to heal by secondary intention. There has yet to be a consensus amongst surgeons regarding optimal management of the donor site. The ideal donor site dressing is one that allows for expeditious healing while minimizing pain and infection. Despite numerous studies demonstrating the superiority of moist wound healing, many surgeons continue to treat STSG donor sites dry, with petroleum-based gauze. In this study, two burn centers performed a retrospective review of burn patients whose STSG donor sites were treated with either Xeroform® or Mepilex® Ag dressings. Infections were documented and in a subgroup analysis of patients, postoperative pain scores were noted and total opiate usage during hospitalization was calculated. Analysis revealed an overall infection rate of 1.2% in the Mepilex® Ag group and 11.4% in the Xeroform® group (p<0.0001). Patients with Xeroform® donor site dressings had increased odds of donor site infection (OR=10.8, p=0.002). In subgroup analysis, there were no significant differences in maximum pain scores between Mepilex® Ag and Xeroform® groups, nor were there differences in opiate usage. STSG donor sites dressed with silver foam dressings have a lower rate of donor site infection relative to those dressed with petroleum-based gauze. Moist donor site dressings such as foam dressings (including Mepilex® Ag) should be the standard of care in STSG donor site wound care.

La greffes de peau mince (GPM) demeure une procédure essentielle dans la chirurgie de brûlure et de reconstruction. La zone donneuse de greffe (ZDG) représente une perte de substance cutanée superficielle, cicatrisant spontanément. Il n'y a pas de consensus concernant la prise en charge optimale de la ZDG. Le pansement idéal de la ZDG doit promouvoir la cicatrisation et réduire la douleur ainsi que le risque infectieux. Malgré les nombreuses publications montrant l'intérêt d'un environnement humide pour la cicatrisation, de nombreux chirurgiens réalisent des pansements secs vaselinés. Cette étude rétrospective effectuée dans 2 CTB compare les pansements de ZDG réalisés au Xéroform® ou au Mepilex Ag®. Les infections ont été documentées et, dans un sous-groupe, les scores de douleur et la consommation d'opiacés au long de l'hospitalisation ont été notés. Les taux d'infection sont de 1,2% dans le groupe Mepilex Ag® et 11,4% avec Xéroform® (p<0,0001). Le risque d'infection de la ZDG est augmenté (OR 10,8 ; p = 0,002) en cas d'utilisation de Xéroform®. Il n'y avait pas de différence de douleur et de consommation d'opiacés entre les 2 groupes. Les ZDG recouvertes d'un pansement hydrocellulaire imprégné d'argent s'infectent moins que celles traitées avec une gaze imprégnée de vaseline. L'utilisation sur les ZDG d'un pansement humide comme une mousse hydrocellulaire (par exemple Mepilex Ag®) devrait devenir la norme.

A systematic review of the impact of contemporary treatment modalities for cervical cancer on women's self-reported health-related quality of life.

PURPOSE: Given the high survival rate of cervical cancer patients, understanding women's health-related quality of life (HRQL) during and after treatment is of major clinical importance. We conducted a systematic review to synthesize all available evidence about the effects of each contemporary treatment modality for cervical cancer on all dimensions of women's HRQL, including symptoms, functioning, and global HRQL. METHODS: We searched four electronic databases from January 2000 to September 2019, cross-referenced and searched by author name for studies of patients treated for cervical cancer that reported patient-reported outcomes (PROs) before treatment and with at least one post-treatment measurement. Two independent reviewers applied inclusion and quality criteria and extracted findings. Studies were categorized by treatment to determine specific treatment effects on PROs. Results were narratively summarized. RESULTS: We found twenty-nine papers reporting 23 studies. After treatments with curative intent for early or locally advanced disease, lymphedema, diarrhea, menopausal symptoms, tight and shorter vagina, pain during intercourse, and sexual worries remained long-term problems; however, sexual activity improved over time. HRQL and psychological distress were impacted during treatment with also worsening of global HRQL but improved 3-6 months after treatment. In patients with metastatic or recurrent disease, pain improved during palliative treatment or remained stable, with no differences in global HRQL found over time. CONCLUSION: Whereas most symptoms worsen during treatment and improve in the first 3 months after completing treatment, symptoms like lymphedema, menopausal symptoms, and sexual worries develop gradually and persist after curative treatment. These findings can be used to inform clinical practice and facilitate communication and shared decision-making. More research is needed in very early cervical cancer and the impact of fertility sparing therapy on PROs.

The prevalence of medical reasons for non-participation in the Scottish breast and bowel cancer screening programmes.

OBJECTIVE: Increasing uptake of cancer screening is a priority for health systems internationally, however, some patients may not attend because they are undergoing active treatment for the cancer of interest or have other medical reasons that mean participation would be inappropriate. This study aims to quantify the proportion of non-participants who have a medical reason for not attending cancer screening. METHODS: Medical reasons for not participating in breast and bowel screening were defined a priori on the basis of a literature review and expert opinion. The notes of 700 patients at two GP practices in Scotland were reviewed, to ascertain the prevalence of medical reasons amongst non-participants. Simple proportions and confidence intervals were calculated. RESULTS: 17.4% of breast and 2.3% of bowel screening non-participants had a medical reason to not participate. The two most common reasons were previous breast cancer follow up (8.86%) and recent mammogram (6.57%). CONCLUSION: These patients may not benefit from screening while also being distressed by receiving an invitation. This issue also makes accurate monitoring and target-setting for improving uptake difficult. Further work is needed to estimate robustly the extent to which medical reasons account for screening non-participation in a larger population.

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung.

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (Ri) from 19 to 7 h and improved organ dysfunction with enhanced alveolar-capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (Ri; 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation.

The origin of pelletal lapilli in explosive kimberlite eruptions.

Kimberlites are volatile-rich magmas from mantle depths of ≥ 150 km and are the primary source of diamonds. Kimberlite volcanism involves the formation of diverging pipes or diatremes, which are the locus of high-intensity explosive eruptions. A conspicuous and previously enigmatic feature of diatreme fills are 'pelletal lapilli'--well-rounded clasts consisting of an inner 'seed' particle with a complex rim, thought to represent quenched juvenile melt. Here we show that these coincide with a transition from magmatic to pyroclastic behaviour, thus offering fundamental insights into eruption dynamics and constraints on vent conditions. We propose that pelletal lapilli are formed when fluid melts intrude into earlier volcaniclastic infill close to the diatreme root zone. Intensive degassing produces a gas jet in which locally scavenged particles are simultaneously fluidised and coated by a spray of low-viscosity melt. A similar origin may apply to pelletal lapilli in other alkaline volcanic rocks, including carbonatites, kamafugites and melilitites.

inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa?

SETTING: Western Cape and Eastern Cape Provinces, South Africa. OBJECTIVE: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene. DESIGN: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis. RESULTS: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%). CONCLUSIONS: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the GenoType® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected.

Increased brain edema in aqp4-null mice in an experimental model of subarachnoid hemorrhage.

We investigated the role of the glial water channel protein aquaporin-4 in brain edema in a mouse model of subarachnoid hemorrhage in which 30 microl of blood was injected into the basal cisterns. Brain water content, intracranial pressure and neurological score were compared in wildtype and aquaporin-4 null mice. We also measured blood-brain barrier permeability, and the osmotic permeability of the glia limitans, one of the routes of edema elimination. Wildtype and aquaporin-4 null mice had comparable baseline brain water content, intracranial pressure and neurological score. At 6 h after blood injection, aquaporin-4 null mice developed more brain swelling than wildtype mice. Brain water content increased by 1.5+/-0.1% vs. 0.5+/-0.2% (Mean+/-Standard Error, P<0.0005) and intracranial pressure by 36+/-5 vs. 21+/-3 mm Hg (P<0.05) above pre-injection baseline, and neurological score was worse at 18.0 vs. 24.5 (median, P<0.05), respectively. Although subarachnoid hemorrhage produced comparable increases in blood-brain barrier permeability in wildtype and aquaporin-4 null mice, aquaporin-4 null mice had a twofold reduction in glia limitans osmotic permeability. We conclude that aquaporin-4 null mice manifest increased brain edema following subarachnoid hemorrhage as a consequence of reduced elimination of excess brain water.

Bilateral versus unilateral cochlear implantation in young children.

OBJECTIVES: To compare the preverbal communication skills of two groups of young implanted children: those with unilateral implantation and those with bilateral implantation. MATERIAL AND METHODS: The study assessed 69 children: 42 unilaterally and 27 bilaterally implanted with age at implantation less than 3 years. The preverbal skills of these children were measured before and 1 year after implantation, using Tait Video Analysis that has been found able to predict later speech outcomes in young implanted children. RESULTS: Before implantation there was no significant difference between the unilateral group and the bilateral group. There was still no difference at 12 months following implantation where vocal autonomy is concerned, but a strongly significant difference between the groups for vocal turn-taking and non-looking vocal turns, the bilateral group outperforming the unilateral group. Regarding gestural turn-taking and gestural autonomy, there was a strongly significant difference between the two groups at the 12 month interval, and also a difference before implantation for gestural autonomy, the unilateral group having the higher scores. Multiple regression of non-looking vocal turns revealed that 1 year following implantation, bilateral implantation contributed to 51% of the variance (p<0.0001), after controlling for the influence of age at implantation and length of deafness which did not reach statistical significance. CONCLUSIONS: Profoundly deaf bilaterally implanted children are significantly more likely to use vocalisation to communicate, and to use audition when interacting vocally with an adult, compared with unilaterally implanted children. These results are independent of age at implantation and length of deafness.

Improved outcome after lumbar microdiscectomy in patients shown their excised disc fragments: a prospective, double blind, randomised, controlled trial.

BACKGROUND: Lumbar microdiscectomy (LMD) is a commonly performed neurosurgical procedure. We set up a prospective, double blind, randomised, controlled trial to test the hypothesis that presenting the removed disc material to patients after LMD improves patient outcome. METHODS: Adult patients undergoing LMD for radiculopathy caused by a prolapsed intervertebral disc were randomised into one of two groups, termed experimental and control. Patients in the experimental group were given their removed disc fragments whereas patients in the control group were not. Patients were unaware of the trial hypothesis and investigators were blinded to patient group allocation. Outcome was assessed between 3 and 6 months after LMD. Primary outcome measures were the degree of improvement in sciatica and back pain reported by the patients. Secondary outcome measures were the degree of improvement in leg weakness, paraesthesia, numbness, walking distance and use of analgesia reported by the patients. RESULTS: Data from 38 patients in the experimental group and 36 patients in the control group were analysed. The two groups were matched for age, sex and preoperative symptoms. More patients in the experimental compared with the control group reported improvements in leg pain (91.5 vs 80.4%; p<0.05), back pain (86.1 vs 75.0%; p<0.05), limb weakness (90.5 vs 56.3%; p<0.02), paraesthesia (88 vs 61.9%; p<0.05) and reduced analgesic use (92.1 vs 69.4%; p<0.02) than preoperatively. CONCLUSION: Presentation of excised disc fragments is a cheap and effective way to improve outcome after LMD.

AQP4 gene deletion in mice does not alter blood-brain barrier integrity or brain morphology.

The glial cell water channel aquaporin-4 (AQP4) plays an important role in brain edema, astrocyte migration, and neuronal excitability. Zhou et al. [Zhou J, Kong H, Hua X, Xiao M, Ding J, Hu G (2008) Altered blood-brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19:1-5] recently reported that AQP4 deletion significantly altered blood-brain barrier integrity and glial fibrillary acidic protein (GFAP) immunoreactivity in their AQP4 null mice. Here we describe a detailed characterization of baseline brain properties in our AQP4 null mice, including gross appearance, neuronal, astrocyte and oligodendrocyte characteristics, and blood-brain barrier integrity. Gross anatomical measurements included estimates of brain and ventricle size. Neurons, astrocytes and oligodendrocytes were assessed using the neuronal nuclear marker NeuN, the astrocyte marker GFAP, and the myelin stain Luxol Fast Blue. The blood-brain barrier was studied by electron microscopy and the horseradish peroxidase extravasation technique. There were no differences in brain and ventricle sizes between wild type and AQP4 null mice, nor were there differences in the cerebral cortical density of NeuN positive nuclei, perimicrovessel and glia limitans GFAP immunoreactivity, or the thickness and myelination of the corpus callosum. The ultrastructure of microvessels in the frontal cortex and caudate nucleus of wild type vs. AQP4 null mice was indistinguishable, with features including intact endothelial tight junctions, absence of perimicrovessel astrocyte foot process edema, and absence of horseradish peroxidase extravasation. In contrast to the report by Zhou et al. (2008), our data show that AQP4 deletion in mice does not produce major structural abnormalities in the brain.

Current neurosurgical trainees' perception of the European Working Time Directive and shift work.

The introduction of the shift system in response to the European Working Time Directive has had an enormous impact on the running of neurosurgical units in the UK. This study seeks to establish what provisions are currently in place for out of hours cover and what has been the effect of the introduction of shifts in three main areas: patient safety, training and 'work/life balance'. The on-call registrar at each UK neurosurgical unit was contacted by telephone. Data regarding current emergency provision were sought. Registrars who had worked both on-calls and the shift system during their career as a neurosurgical registrar were asked to make a comparison. Data were collected from all 33 UK units. Twenty-two still use a traditional 24-h on-call system. Twenty-one on-call rotas were classed as non-resident although 12/21 of those officially on non-resident rotas were in fact resident whilst on call. Twenty-two registrars had worked both systems as a neurosurgical registrar. Twenty-one (95.45%) felt that traditional on-calls gave better clinical exposure. Twenty-one (95.45%) felt that on-calls allowed the provision of better patient care. Nineteen (86.36%) felt that on-calls were safer. Thirteen (59.09%) reported that they were more tired when doing shift work than on-calls. Fourteen (63.63%) found that the on-call system gives more useful spare time and more time to deal with family commitments. Current neurosurgery registrars feel the shift system is less safe, harmful to training and worse in terms of work/life balance. More than one-third of units are claiming to have non-resident on-call systems in order to appear compliant with EWTD when registrars are in fact resident.

Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases.

Glioblastoma is the most common primary brain tumour. The aim of this study was to determine trends in survival over a 12-year period. Survival data were collected retrospectively for 625 patients who had surgery for histologically-confirmed glioblastoma between 1993 and 2004 in a single centre. Data including age, sex, preoperative Karnofsky performance score, tumour site, date of surgery, and type of surgical and adjuvant treatment were collected. Overall median survival was 189 days; there was no significant change in survival over 12 years. Multivariate analysis identified the following independent positive prognostic factors: age <60 years (p < 0.0005), Karnofsky score > or = 70 (p < 0.0001), tumour debulking, rather than biopsy (p < 0.001), right-sided lesion (p < 0.05), unilateral tumour (p < 0.05) and radiotherapy (p < 0.0001). Despite neurosurgical advances, the survival of patients with glioblastoma has not changed for more than a decade. Although, overall, glioblastoma has a short survival, our data show that individual patient survival is heterogeneous.

Deaf children with cochlear implants before the age of 1 year: comparison of preverbal communication with normally hearing children.

OBJECTIVES: To compare preverbal behaviors of deaf children implanted under 1 year of age with age-matched hearing children. METHODS: The study assessed 20 children; 10 deaf children implanted under 1 year of age and 10 normally hearing children of the same age. Preverbal skills were measured before, 6 months, and 1 year after implantation, using Tait Video Analysis that is able to predict later speech outcomes in young implanted children. RESULTS: Regarding vocal turns, the normally hearing group outperformed the implanted group although the latter children became quite vocal, nearly 60% of their turns being taken in this way. The mean vocal autonomy in implanted children, 1 year after implantation, was very close to the respective of hearing children (38.5 versus 43.5). Regarding the non-looking vocal turns, by the 12-month interval, hearing children had somewhat higher scores than implanted children, but the difference was not significant and the increase in implanted children was much higher (40-fold increase versus 4-fold increase). However, implanted children were more likely to use silent communication than hearing children, although gestural turns were decreasing with time. CONCLUSIONS: The small numbers in this study, although two of the largest European cochlear implant centers were combined to recruit such young implantees, led us to be cautious in interpreting the results. However, it seems that in deaf implanted children under 1 year of age, some preverbal communication behaviors are developing to an extent (although at a somewhat lower level) not significantly different from those of age-matched normally hearing children.

The use and reliability of Tait video analysis in assessing preverbal language skills in profoundly deaf and normally hearing children under 12 months of age.

BACKGROUND: Assessment measures in evaluating preverbal skills and their progress in very young deaf children are lacking. However, their importance is highlighted by the recent trend of implanting children under 1 year of age. Tait video analysis is a technique for assessing preverbal communication behaviours in very young children with hearing impairment and has been found to be strongly related to speech discrimination and intelligibility outcomes post-implantation. AIM: To assess feasibility and inter-user reliability of Tait video analysis in assessing preverbal communication skills in children under 1 year of age. MATERIAL AND METHODS: Ten children (five profoundly deaf and five normally hearing) under 1 year of age were assessed by Tait video analysis. Three observers analysed the samples independently, according to the established protocol. RESULTS: There was complete agreement on 305 judgements and 8 discrepancies between observers over all the measures. Four of the discrepancies occurred in the samples of deaf children and four in the normally hearing samples. Statistical analysis revealed that the correlation coefficients between the different observers were extremely high ranging from 0.94 to 1 (perfect agreement). All of them were found to be statistically significant (p<0.01). CONCLUSION: The very high rate of inter-observer reliability suggests that the video recordings of children under 12 months can be scored consistently, and Tait video analysis is therefore a valid method of monitoring the development of vocal and auditory preverbal skills in very young deaf children, either following cochlear implantation or using acoustic hearing aids.

How much can be concluded from the International Subarachnoid Aneurysm Trial (ISAT)?

Recently published data from the International Subarachnoid Aneurysm Trial (ISAT) shows that for patients enrolled in the trial there is a 7.4% reduction in the incidence of death or dependency at 1 year if they undergo coiling, rather than clipping. Furthermore, extrapolation of longer-term follow-up data for patient mortality appears to suggest that this advantage will be maintained in the longer term. Based on a reassessment of the published data, the authors note: (1) the incidence of rebleeding following treatment is approximately three times higher in the coiled group (p<0.001); (2) the need for aneurysm retreatment is likely to be higher in the coiled group; (3) trends in longer-term mortality data are not a reliable basis for predicting future outcomes of the trial; (4) trends in longer-term morbidity data are more reliable and suggest that the advantage of coiling diminishes with time; (5) The absence of up-to-date published rates of aneurysm retreatment and of longer-term rates of death or dependence makes ISAT extremely hard to interpret. It is far from clear that the early advantage of coiling will be maintained in the future and, hence, longer follow-up is required. Treatment of aneurysms is a continually evolving field and there is currently no other major source of information concerning management of aneurysms. For these reasons the authors recommend the instigation of a national aneurysm registry to prospectively collect data.

Age at implantation and development of vocal and auditory preverbal skills in implanted deaf children.

BACKGROUND: Preverbal vocal and auditory skills are essential precursors of spoken language development and they have been shown previously to predict later speech perception and production outcomes in young implanted deaf children. OBJECTIVES: To assess the effect of age at implantation on the development of vocal and auditory preverbal skills in implanted children. METHODS: The study assessed 99 children, 33 in each of three groups (those implanted between 1 and 2 years; 2 and 3 years; and 3 and 4 years). Preverbal skills were measured in three areas: turn taking, autonomy and auditory awareness of spoken language, using the Tait video analysis method. RESULTS: The youngest implanted group made an exceptional progress outperforming in all measures the two other groups (p<0.01), 6 and 12 months post-implantation, whereas there was no such difference before implantation. In the youngest group there was also significantly greater use of an auditory/oral style of communication: 85% of the group by 12 months post-implantation compared with 30% and 18% of the two older groups. CONCLUSIONS: Vocal and auditory preverbal skills develop much more rapidly in children implanted between 1 and 2 years in comparison with older implanted children and reach a significantly higher level by 6 and 12 months post-implantation. In addition, younger implanted children are significantly more likely by 12 months post-implantation to adopt an auditory/oral mode of communication. These findings favour cochlear implantation as early as between 1 and 2 years, provided that correct diagnosis and adequate hearing-aid trial have been achieved.

Audit of neurosurgery senior house officer training in the United Kingdom and Eire: a postal survey.

An audit was performed to describe the current training conditions of senior house officers in neurosurgery in the UK and Eire. A postal questionnaire was sent to all neurosurgery senior house officers in a 6-month training period between February and August 2003. The questionnaire covered most aspects of working pattern, training and job satisfaction by the end of the 6-month post. The results from the audit showed that there are deficiencies in certain areas of the current system being employed for senior house officer training. Improvements to this training system in line with the establishment of a generic neurosciences training programme will benefit future surgical trainees.

Intracellular cyclic nucleotide analogues inhibit in vitro mitogenesis and activation of fibroblasts derived from obstructed rat kidneys.

As several studies indirectly suggest that inhibiting the intracellular breakdown of cyclic nucleotides may inhibit fibrogenesis, this study used membrane permeable cyclic nucleotide analogues to examine the role of cAMP and cGMP signaling pathways in the regulation of renal fibroblast function. Fibroblasts were isolated by explant outgrowth culture of rat kidneys post unilateral ureteric obstruction. Subcultured cells were exposed to 10- 1,000 microM of the cyclic nucleotide analogues 8-bromo-cAMP (8br-cAMP) and 8-bromo-cGMP (8br-cGMP). Functional parameters examined included mitogenesis (thymidine incorporation), collagen synthesis (proline incorporation), myofibroblast differentiation (Western blotting for alpha-smooth muscle actin; alpha-SMA) and expression of CTGF (Northern blotting), a TGF-beta(1)-driven immediate early response gene. Serum-stimulated mitogenesis was decreased 27 +/- 4% by 100 microM 8br-cAMP (p < 0.01), 49 +/- 6% by 1,000 microM 8br-cAMP (p < 0.001) and 43 +/- 7% by 1,000 microM 8br-cGMP (p < 0.01). 1,000 microM 8br-cAMP and 8br-cGMP reduced basal collagen synthesis by 80 +/- 5 and 60 +/- 21% respectively (both p < 0.05). Maximum dose of 8br-cAMP but not 8br-cGMP inhibited basal expression of the differentiation marker alpha-SMA by 43 +/- 33 (p < 0.05), resulted in a more rounded cell morphology and reduced expression of CTGF by 39 +/- 24% (p < 0.05). Measurement of mitochondrial activity confirmed that effects were independent of cell toxicity. In conclusion, cyclic nucleotides inhibit fibrogenesis in vitro. Strategies which elevate intracellular cyclic nucleotide concentrations may therefore be therapeutically valuable in preventing the proliferation and activation of fibroblasts in progressive renal disease.