Primary care diagnostic and treatment pathways in Dutch women with urinary incontinence.

OBJECTIVE: To investigate how GPs manage women with urinary incontinence (UI) in the Netherlands and to assess whether this is in line with the relevant Dutch GP guideline. Because UI has been an underreported and undertreated problem for decades despite appropriate guidelines being created for general practitioners (GPs). DESIGN: Retrospective cohort study. SETTING: Routine primary care data for 2017 in the Netherlands. SUBJECTS: We included the primary care records of women aged 18-75 years with at least one contact registered for UI, and then extracted information about baseline characteristics, diagnosis, treatment, and referral to pelvic physiotherapy or secondary care. RESULTS: In total, 374 records were included for women aged 50.3 ± 15.1 years. GPs diagnosed 31.0%, 15.2%, and 15.0% women with stress, urgency, or mixed UI, respectively; no diagnosis of type was recorded in 40.4% of women. Urinalysis was the most frequently used diagnostic test (42.5%). Education was the most common treatment, offered by 17.9% of GPs; however, no treatment or referral was reported in 15.8% of cases. As many as 28.7% and 21.7% of women were referred to pelvic physiotherapy and secondary care, respectively. CONCLUSION: Female UI is most probably not managed in line with the relevant Dutch GP guideline. It is also notable that Dutch GPs often fail to report the type of UI, to use available diagnostic approaches, and to provide appropriate education. Moreover, GPs referred to specialists too often, especially for the management of urgency UI.Key pointsUrinary incontinence (UI) has been an underreported and undertreated problem for decades. Despite various guidelines, UI often lies outside the GPs comfort zone.•According to this study: general practitioners do not treat urinary incontinence according to guidelines.•The type of incontinence is frequently not reported and diagnostic approaches are not fully used.•We believe that increased awareness will help improve treatment and avoidable suffering.

In interaction with gender a common CYP3A4 polymorphism may influence the survival rate of chemotherapy for childhood acute lymphoblastic leukemia.

CYP3A4 has an important role in the metabolisms of many drugs used in acute lymphoblastic leukemia (ALL) therapy; still, there are practically no publications about the role of CYP3A4 polymorphisms in ALL pharmacogenomics. We genotyped eight common single-nucleotide polymorphisms (SNPs) in the CYP3A4 and CYP3A5 genes in 511 children with ALL and investigated whether they influenced the survival of the patients. We involved additional 127 SNPs in 34 candidate genes and searched for interactions with respect to the survival rates. Significant association between the survival rates and the common rs2246709 SNP in the CYP3A4 gene was observed. The gender of the patients and the rs1076991 in the MTHFD1 gene strongly influenced this effect. We calculated new risk assessments involving the gender-rs2246709 interaction and showed that they significantly outperformed the earlier risk-group assessments at every time point. If this finding is confirmed in other populations, it can have a considerable prognostic significance.

Managing children with daytime urinary incontinence: a survey of Dutch general practitioners.

BACKGROUND: In the Netherlands, parents of children with daytime urinary incontinence (UI) first consult general practitioners (GPs). However, GPs need more specific guidelines for daytime UI management, resulting in care and referral decisions being made without clear guidance. OBJECTIVES: We aimed to identify Dutch GP considerations when treating and referring a child with daytime UI. METHODS: We invited GPs who referred at least one child aged 4-18 years with daytime UI to secondary care. They were asked to complete a questionnaire about the referred child and the management of daytime UI in general. RESULTS: Of 244 distributed questionnaires, 118 (48.4%) were returned by 94 GPs. Most reported taking a history and performing basic diagnostic tests like urine tests (61.0%) and physical examinations (49.2%) before referral. Treatment mostly involved lifestyle advice, with only 17.8% starting medication. Referrals were usually at the explicit wish of the child/parent (44.9%) or because of symptom persistence despite treatment (39.0%). GPs usually referred children to a paediatrician (n = 99, 83.9%), only referring to a urologist in specific situations. Almost half (41.4%) of the GPs did not feel competent to treat children with daytime UI and more than half (55.7%) wanted a clinical practice guideline. In the discussion, we explore the generalisability of our findings to other countries. CONCLUSION: GPs usually refer children with daytime UI to a paediatrician after a basic diagnostic assessment, usually without offering treatment. Parental or child demand is the primary stimulus for referral.

Prediction of peak pressure from clinical and radiological measurements in patients with diabetes.

BACKGROUND: Various structural and functional factors of foot function have been associated with high local plantar pressures. The therapist focuses on these features which are thought to be responsible for plantar ulceration in patients with diabetes. Risk assessment of the diabetic foot would be made easier if locally elevated plantar pressure could be indicated with a minimum set of clinical measures. METHODS: Ninety three patients were evaluated through vascular, orthopaedic, neurological and radiological assessment. A pressure platform was used to quantify the barefoot peak pressure for six forefoot regions: big toe (BT) and metatarsals one (MT-1) to five (MT-5). Stepwise regression modelling was performed to determine which set of the clinical and radiological measures explained most variability in local barefoot plantar peak pressure in each of the six forefoot regions. Comprehensive models were computed with independent variables from the clinical and radiological measurements. The difference between the actual plantar pressure and the predicted value was examined through Bland-Altman analysis. RESULTS: Forefoot pressures were significant higher in patients with neuropathy, compared to patients without neuropathy for the whole forefoot, the MT-1 region and the MT-5 region (respectively 138 kPa, 173 kPa and 88 kPa higher: mean difference). The clinical models explained up to 39 percent of the variance in local peak pressures. Callus formation and toe deformity were identified as relevant clinical predictors for all forefoot regions. Regression models with radiological variables explained about 26 percent of the variance in local peak pressures. For most regions the combination of clinical and radiological variables resulted in a higher explained variance. The Bland and Altman analysis showed a major discrepancy between the predicted and the actual peak pressure values. CONCLUSION: At best, clinical and radiological measurements could only explain about 34 percent of the variance in local barefoot peak pressure in this population of diabetic patients. The prediction models constructed with linear regression are not useful in clinical practice because of considerable underestimation of high plantar pressure values. Identification of elevated plantar pressure without equipment for quantification of plantar pressure is inadequate. The use of quantitative plantar pressure measurement for diabetic foot screening is therefore advocated.

Daily-life activities and in-shoe forefoot plantar pressure in patients with diabetes.

OBJECTIVE: To assess differences regarding in-shoe forefoot plantar pressure (PP) in patients with diabetes during various daily-life activities. RESEARCH DESIGN AND METHODS: In-shoe PP was measured in 93 patients during: level walking, ramp and stair walking, turning in different settings and while performing the Up & Go test. Separate PPs were determined for the big toe and metatarsal (mt) regions one to five. RESULTS: Across all activities, similar PPs were measured in the big toe and mt-1 to mt-3 region. Lower PPs were measured in mt-4 and mt-5 region. PPs during level walking were mostly higher when compared to the other activities (p

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress.

One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression- and anxiety-related phenotypes. In addition, a Bayesian systems-based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone.

Testing the proficiency to distinguish locations with elevated plantar pressure within and between professional groups of foot therapists.

BACKGROUND: Identification of locations with elevated plantar pressures is important in daily foot care for patients with rheumatoid arthritis, metatarsalgia and diabetes. The purpose of the present study was to evaluate the proficiency of podiatrists, pedorthists and orthotists, to distinguish locations with elevated plantar pressure in patients with metatarsalgia. METHODS: Ten podiatrists, ten pedorthists and ten orthotists working in The Netherlands were asked to identify locations with excessively high plantar pressure in three patients with forefoot complaints. Therapists were instructed to examine the patients according to the methods used in their everyday clinical practice. Regions could be marked through hatching an illustration of a plantar aspect. A pressure sensitive platform was used to quantify the dynamic bare foot plantar pressures and was considered as 'Gold Standard' (GS). A pressure higher than 700 kPa was used as cut-off criterion for categorizing peak pressure into elevated or non-elevated pressure. This was done for both patient's feet and six separate forefoot regions: big toe and metatarsal one to five. Data were analysed by a mixed-model ANOVA and Generalizability Theory. RESULTS: The proportions elevated/non-elevated pressure regions, based on clinical ratings of the therapists, show important discrepancies with the criterion values obtained through quantitative plantar pressure measurement. In general, plantar pressures in the big toe region were underrated and those in the metatarsal regions were overrated. The estimated method agreement on clinical judgement of plantar pressures with the GS was below an acceptable level: i.e. all intraclass correlation coefficient's equal or smaller than .60. The inter-observer agreement for each discipline demonstrated worrisome results: all below .18. The estimated mutual agreements showed that there was virtually no mutual agreement between the professional groups studied. CONCLUSION: Identification of elevated plantar pressure through clinical evaluation is difficult, insufficient and may be potentially harmful. The process of clinical plantar pressure screening has to be re-evaluated. The results of this study point towards the merit of quantitative plantar pressure measurement for clinical practice.

Casting methods and plantar pressure: effects of custom-made foot orthoses on dynamic plantar pressure distribution.

Foot orthoses are widely used to treat various foot problems. A literature search revealed no publications on differences in plantar pressure distribution resulting from casting methods for foot orthoses. Four casting methods were used for construction of orthoses. Two foam box techniques were used: accommodative full weightbearing method (A) and functional semiweightbearing method (B). Also, two suspension plaster casting techniques were used: accommodative casting (C) and functional subtalar joint neutral position (Root) method (D). Their effects on contact area, plantar pressure, and walking convenience were evaluated. All orthoses increased the total contact area (mean, 17.4%) compared with shoes without orthoses. Differences in contact areas between orthoses for total plantar surface were statistically significant. Peak pressures for the total plantar surface were lower with orthoses than without orthoses (mean, 22.8%). Among orthoses, only the difference between orthoses A and B was statistically significant. Differences between orthoses for the forefoot were small and not statistically significant. The gait lines of the shoe without an insole and of the accommodative orthoses are more medially located than those of functional orthoses. Walking convenience in the shoe was better rated than that with orthoses. There were no differences in perception of walking convenience between orthoses A, B, and C. Orthosis D had the lowest convenience rating. The four casting methods resulted in differences between orthoses with respect to contact areas and walking convenience but only slight differences in peak pressures.

Total contact casting of the diabetic foot in daily practice: a prospective follow-up study.

OBJECTIVE: A limited number of clinical trials have shown that the total contact cast (TCC) is an effective treatment in neuropathic, noninfected, and nonischemic foot ulcers. In this prospective data collection study, we assessed outcome and complications of TCC treatment in neuropathic patients with and without peripheral arterial disease (PAD) or (superficial) infection. RESEARCH DESIGN AND METHODS: Ninety-eight consecutive patients selected for casting were followed until healing; all had polyneuropathy, 44% had PAD, and 29% had infection. Primary outcomes were percentage healed with a cast, time to heal, and number of complications. RESULTS: Ninety percent of all nonischemic ulcers without infection and 87% with infection healed in the cast (NS). In patients with PAD but without critical limb ischemia, 69% of the ulcers without infection and 36% with infection healed (P < 0.01). In multivariate analyses, PAD, infection, and heel ulcers were associated with a lower percentage healed (all P < 0.05). Median duration of cast treatment was 34 days. New ulcers, all superficial, developed in 9% and preulcerative lesions in 28% of the patients; these skin lesions healed in the cast within a maximum of 13 days. CONCLUSIONS: In comparison to pure neuropathic ulcers, ulcers with moderate ischemia or infection can be treated effectively with casting. However, when both PAD and infection are present or the patient has a heel ulcer, outcome is poor and alternative strategies should be sought. The high rate of preulcerative lesions stresses the importance of close monitoring during TCC treatment.

Comparison of foot orthoses made by podiatrists, pedorthists and orthotists regarding plantar pressure reduction in The Netherlands.

BACKGROUND: There is a need for evidence of clinical effectiveness of foot orthosis therapy. This study evaluated the effect of foot orthoses made by ten podiatrists, ten pedorthists and eleven orthotists on plantar pressure and walking convenience for three patients with metatarsalgia. Aims were to assess differences and variability between and within the disciplines. The relationship between the importance of pressure reduction and the effect on peak pressure was also evaluated. METHODS: Each therapist examined all three patients and was asked to rate the 'importance of pressure reduction' through a visual analogue scale. The orthoses were evaluated twice in two sessions while the patient walked on a treadmill. Plantar pressures were recorded with an in-sole measuring system. Patients scored walking convenience per orthosis. The effects of the orthoses on peak pressure reduction were calculated for the whole plantar surface of the forefoot and six regions: big toe and metatarsal one to five. RESULTS: Within each discipline there was an extensive variation in construction of the orthoses and achieved peak pressure reductions. Pedorthists and orthotists achieved greater maximal peak pressure reductions calculated over the whole forefoot than podiatrists: 960, 1020 and 750 kPa, respectively (p < .001). This was also true for the effect in the regions with the highest baseline peak pressures and walking convenience rated by patients A and B. There was a weak relationship between the 'importance of pressure reduction' and the achieved pressure reduction for orthotists, but no relationship for podiatrists and pedorthotists. CONCLUSION: The large variation for various aspects of foot orthoses therapy raises questions about a consistent use of concepts for pressures management within the professional groups.

Three-dimensional reconstruction of magnetic resonance images of a displaced flexor hallucis longus tendon in hallux valgus.

By using three-dimensional magnetic resonance image reconstruction, lateral displacement of the flexor hallucis longus tendon and sesamoid bones was made clearly visible in a living patient. This finding supports a biomechanical model related to disturbed muscle balance at the first metatarsophalangeal joint, which could play an important role in the pathogenesis of hallux valgus and metatarsus primus varus.

Probabilistic graphical models for computational biomedicine.

BACKGROUND: As genomics becomes increasingly relevant to medicine, medical informatics and bioinformatics are gradually converging into a larger field that we call computational biomedicine. OBJECTIVES: Developing a computational framework that is common to the different disciplines that compose computational biomedicine will be a major enabler of the further development and integration of this research domain. METHODS: Probabilistic graphical models such as Hidden Markov Models, belief networks, and missing-data models together with computational methods such as dynamic programming, Expectation-Maximization, data-augmentation Gibbs sampling, and the Metropolis-Hastings algorithm provide the tools for an integrated probabilistic approach to computational biomedicine. RESULTS AND CONCLUSIONS: We show how graphical models have already found a broad application in different fields composing computational biomedicine. We also indicate several challenges that lie at the interface between medical informatics, statistical genomics, and bioinformatics. We also argue that graphical models offer a unified framework making it possible to integrate in a statistically meaningful way multiple models ranging from the molecular level to cellular and to clinical levels. Because of their versatility and firm statistical underpinning, we assert that probabilistic graphical models can serve as the lingua franca for many computationally intensive approaches to biology and medicine. As such, graphical models should be a foundation of the curriculum of students in these fields. From such a foundation, students could then build towards specific computational methods in medical informatics, medical image analysis, statistical genetics, or bioinformatics while keeping the communication open between these areas.

A comparison of hallux valgus angles assessed with computerised plantar pressure measurements, clinical examination and radiography in patients with diabetes.

BACKGROUND: Hallux valgus deformity is a common musculoskeletal foot disorder with a prevalence of 3.5% in adolescents to 35.7% in adults aged over 65 years. Radiographic measurements of hallux valgus angles (HVA) are considered to be the most reproducible and accurate assessment of HVA. However, in European countries, many podiatrists do not have direct access to radiographic facilities. Therefore, alternative measurements are desired. Such measurements are computerised plantar pressure measurement and clinical goniometry. The purpose of this study was to establish the agreement of these techniques and radiographic assessments. METHODS: HVA was determined in one hundred and eighty six participants suffering from diabetes. Radiographic measurements of HVA were performed with standardised static weight bearing dorsoplantar foot radiographs. The clinical goniometry for HVA was measured with a universal goniometer. Computerised plantar pressure measurement for HVA was executed with the EMED SF-4® pressure platform and Novel-Ortho-Geometry software. The intra-class correlation coefficients (ICC) and levels of agreement were analysed using Bland & Altman plots. RESULTS: Comparison of radiographic measurements to clinical goniometry for HVA showed an intraclass correlation coefficient (ICC) of 0.81 (95% confidence interval, 0.76 to 0.86; p<0.001). Radiographic measurement versus computerised plantar pressure measurement showed an ICC of 0.59 (95% confidence interval, 0.49 to 0.68; p<0.001). In addition, clinical goniometry versus computerised plantar pressure measurement showed an ICC of 0.77 (95% confidence interval, 0.70 to 0.82; p<0.001). The systematic difference of the computerised plantar pressure measurement compared with radiographic measurement and clinical goniometry was 7.0 degrees (SD 6.8) and 5.2 degrees (SD 5.0), respectively. The systemic difference of radiographic measurements compared with clinical goniometry was 1.8 degrees (SD 5.0). CONCLUSIONS: The agreement of computerised plantar pressure measurement and clinical goniometry for HVA compared to radiographic measurement of HVA is unsatisfactory. Radiographic measurements of HVA and clinical goniometry for HVA yield better agreement compared to radiographic measurements and computerised plantar pressure measurement. The traditional radiographic measurement techniques are strongly recommended for the assessment of HVA.

Multi-aspect candidates for repositioning: data fusion methods using heterogeneous information sources.

Drug repositioning, an innovative therapeutic application of an old drug, has received much attention as a particularly costeffective strategy in drug R&D Recent work has indicated that repositioning can be promoted by utilizing a wide range of information sources, including medicinal chemical, target, mechanism, main and side-effect-related information, and also bibliometric and taxonomical fingerprints, signatures and knowledge bases. This article describes the adaptation of a conceptually novel, more efficient approach for the identification of new possible therapeutic applications of approved drugs and drug candidates, based on a kernel-based data fusion method. This strategy includes (1) the potentially multiple representation of information sources, (2) the automated weighting and statistically optimal combination of information sources, and (3) the automated weighting of parts of the query compounds. The performance was systematically evaluated by using Anatomical Therapeutic Chemical Classification System classes in a cross-validation framework. The results confirmed that kernel-based data fusion can integrate heterogeneous information sources significantly better than standard rank-based fusion can, and this method provides a unique solution for repositioning; it can also be utilized for de novo drug discovery. The advantages of kernel-based data fusion are illustrated with examples and open problems that are particularly relevant for pharmaceutical applications.

Patient and professional delay in the referral trajectory of patients with diabetic foot ulcers.

AIMS: A cohort study investigated referral and treatment trajectories of patients with diabetic foot ulceration consulting podiatrists. The study aims were to quantify patient, professional and treatment (=total) delay and to identify relationships between patient- or professional-related characteristics, delays or ulcer healing time. METHODS: Ten podiatrists specialising in diabetes care included 54 consecutive adults with diabetic foot ulceration. Assessments were performed retrospectively (e.g. delays) and prospectively (12 weeks). RESULTS: Median (SD; range) patient delay was 3.0 days (50.6; 0-243), professional delay 7.0 days (63.4; 0-279) and treatment delay 20.5 days (97.3; 0-522). 57% of patients took >2 weeks before visiting a podiatrist. Ulcers healed in 67% of patients in 49.0 days (90.2; 4-408). The number of health care professionals in the referral trajectory was positively related to treatment delay (p<0.01) and to ulcer healing time (p<0.01). Professional delay and treatment delay was positively correlated with the duration of the podiatric treatment (p<0.05). Patient awareness of ulceration risk tended to decrease the healing time. CONCLUSIONS: Patients with diabetic foot ulcers presented small median delays in the referral trajectory to podiatrists specialising in diabetes. The study results suggest that reducing the number of health care professionals in the referral trajectory might decrease treatment delay and ulcer healing time. Also improving patient awareness of ulceration risk might be beneficial for the healing time.

Arteriolar biomechanics in a rat polycystic ovary syndrome model - effects of parallel vitamin D3 treatment.

UNLABELLED: To clarify the effects of dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) on arteriolar biomechanics in a rat model and the possible modulatory role of vitamin D3. METHODS AND RESULTS: The PCOS model was induced in female Wistar rats by ten-weeks DHT treatment. Arteriolar biomechanics was tested in arterioles by pressure arteriography in control as well as DHT- and DHT with vitamin D3-treated animals in contracted and passive conditions. Increased wall stress and distensibility as well as increased vascular lumen were detected after DHT treatment. Concomitant vitamin D3 treatment lowered the mechanical load of the arterioles and restored the vascular diameter. CONCLUSION: The hyperandrogenic state resulted in more rigid, less flexible arteriolar walls with increased vascular lumen compared with controls. DHT treatment caused eutrophic remodelling of gracilis arteriole. These prehypertensive alterations caused by chronic DHT treatment were mostly reversed by concomitant vitamin D3 administration.

Is the incidence of appendicitis reduced in patients with sickle cell disease?

BACKGROUND: Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributable to vasoocclusion. Experience at a single institution suggested that appendicitis was a rare cause of abdominal symptoms in this population. OBJECTIVE: We sought to determine whether the incidence of appendicitis was significantly lower in patients with SCD than in the population at large. METHODS: A 17-year retrospective chart review was performed at Rainbow Babies and Children's Hospital, Cleveland, OH, to determine the approximate incidence of acute appendicitis (AA) in patients with SCD. In addition, we performed a statistical analysis comparing the incidence of AA among SCD patients enrolled in the Cooperative Study of Sickle Cell Disease with that in the general population. RESULTS: Only two patients with SCD with pathologically confirmed AA were identified among approximately 200 patients followed at our institution during a 17-year period ( approximately 3500 patient-years), yielding an incidence rate of 5.7 cases per 10 000 patient-years. Among 3765 patients with SCD enrolled in the Cooperative Study of Sickle Cell Disease followed for a mean of 5.3 years (19 886 patient-years), a maximum of 9 cases of AA were identified, yielding an incidence rate of 4.5 cases per 10 000 patient-years. Based on data from the National Hospital Discharge Survey of 1978 to 1981, the incidence rate of AA in the general population (0 to 44 years of age) is approximately 16 per 10 000 patient-years. Paired t test analysis demonstrated a highly significant difference (P < .001) when comparing the incidence of AA among patients enrolled in the Cooperative Study of Sickle Cell Disease and the population at large. CONCLUSION: AA is an unusual event in patients with SCD. The likelihood of developing appendicitis in SCD patients is less than one third of that for the population at large. Conservative therapy is warranted in the large majority of patients with SCD who present with acute abdominal pain. Surgical exploration is best limited to patients with clear evidence of potential surgical pathology or progressive findings during a period of observation. The biologic basis of our findings remains unknown.

Evaluation of the vector space representation in text-based gene clustering.

Thanks to its increasing availability, electronic literature can now be a major source of information when developing complex statistical models where data is scarce or contains much noise. This raises the question of how to deeply integrate information from domain literature with experimental data. Evaluating what kind of statistical text representations can integrate literature knowledge in clustering still remains an unsufficiently explored topic. In this work we discuss how the bag-of-words representation can be used successfully to represent genetic annotation and free-text information coming from different databases. We demonstrate the effect of various weighting schemes and information sources in a functional clustering setup. As a quantitative evaluation, we contrast for different parameter settings the functional groupings obtained from text with those obtained from expert assessments and link each of the results to a biological discussion.

Flow cytometric assay of phagocytic activity of human neutrophils and monocytes in whole blood by neutral red uptake.

In a new, simple, and fast flow-cytometric method for the simultaneous measurement of phagocytic activity of human neutrophils and monocytes in whole blood, the fluorescence capability of the well-known vital stain, neutral red was used. The incubation of 0.5 ml heparinized human blood with the phagocytic stimulus of zymosan dose- and time-dependently increased the percentage and the red fluorescence intensity of both neutrophils (4.3 +/- 1.2 times) and monocytes (2.7 +/- 0.7 times) measured cytofluorimetrically. Decreased uptake of neutral red was observed in a patient with phagocytic disorder, based upon impaired engulfment of particles and production of reactive oxygen species. In a patient with chronic granulomatosis, however, no decrease of neutral red uptake was measured. Platelet activating factor and phorbol myristate acetate were also able to increase the uptake of neutral red by both monocytes and neutrophils, but to a lesser extent than zymosan. The advantage of this method is the possibility for the simultaneous measurement of phagocytic activities of monocytes and neutrophils stimulated by either particles or soluble activators. This method is suitable for the selective measurement of activation processes not related to the production of free radicals in the phagocytes.