Objective Quantitative Assessment Research Articles

Thalamic metabolism and neurological outcome after traumatic brain injury. A voxel-based morphometric FDG-PET study

Objective To study the relationship between thalamic metabolism and neurological outcome in patients who had sustained a traumatic brain injury (TBI). Methods Nineteen patients who had sustained a severe TBI and ten control subjects were included in this study. Six of the 19 patients had a low level of consciousness (vegetative state or minimally conscious state), while thirteen showed normal consciousness. All patients underwent an 18F-FDG PET, 459.4 ± 470.9 days after the TBI. The FDG-PET images were normalised in intensity, with a metabolic template being created from data derived from all subjects. The thalamic trace was generated automatically with a mask of the region of interest to evaluate its metabolism. A comparison between the two groups was carried out by a two sample voxel-based T-test, under the General Linear Model (GLM) framework. Results Patients with low consciousness had lower thalamic metabolism (MNI-Talairach coordinates: 12, —24, 18; T=4.1) than patients with adequate awareness (14, —28, 6; T=5.5). Control subjects showed the greatest thalamic metabolism compared to both patients groups. These differences in metabolism were more pronounced in the internal regions of the thalamus. Conclusions The applied method may be a useful ancillary tool to assess neurological outcomes after a TBI, since it permits an objective quantitative assessment of metabolic function for groups of subjects. Our results confirm the vulnerability of the thalamus to suffering the effects of the acceleration-deceleration forces generated during a TBI. It is hypothesized that patients with low thalamic metabolism represent a subset of subjects highly vulnerable to neurological and functional disability after TBI.

Metabolismo talámico y situación neurológica tras un traumatismo craneoencefálico. Estudio mediante PET-FDG y morfometría basada en vóxel

ObjectiveTo study the relationship between thalamic metabolism and neurological outcome in patients who had sustained a traumatic brain injury (TBI). MethodsNineteen patients who had sustained a severe TBI and ten control subjects were included in this study. Six of the 19 patients had a low level of consciousness (vegetative state or minimally conscious state), while thirteen showed normal consciousness. All patients underwent a PET with 18F-FDG, 459.4 ± 470.9 days after the TBI. The FDG-PET images were normalized in intensity, with a metabolic template being created from data derived from all subjects. The thalamic trace was generated automatically with a mask of the region of interest in order to evaluate its metabolism. A comparison between the two groups was carried out by a two sample voxel-based T-test, under the General Linear Model (GLM) framework. ResultsPatients with low consciousness had lower thalamic metabolism (MNI-Talairach coordinates: 12, -24, 18; T=4.1) than patients with adequate awareness (14, -28, 6; T=5.5). Control subjects showed the greatest thalamic metabolism compared to both patients groups. These differences in metabolism were more pronounced in the internal regions of the thalamus. ConclusionsThe applied method may be a useful ancillary tool to assess neurological outcomes after a TBI, since it permits an objective quantitative assessment of metabolic function for groups of subjects. Our results confirm the vulnerability of the thalamus to suffering the effects of the acceleration-deceleration forces generated during a TBI. It is hypothesized that patients with low thalamic metabolism represent a subset of subjects highly vulnerable to neurological and functional disability after TBI.

Is longer duration of proton pump inhibitor trial better for gastroesophageal reflux disease‐related non‐cardiac chest pain?

Is longer duration of proton pump inhibitor trial better for gastroesophageal reflux disease‐related non‐cardiac chest pain?

Quantitative evaluation of balance in patients with spinocerebellar ataxia type 1: A case control study

Objective Quantitative assessment of balance in spinocerebellar ataxia type 1 (SCA1). Background Evaluation of balance in degenerative ataxias is often clinical and subject to bias. Quantification of balance is crucial for evaluating the efficacy of therapeutic and rehabilitative interventions. Methods The subjects were 20 patients (males: 14, females: 6) with genetically positive SCA1 and 20 age and gender matched healthy subjects. Ataxia was rated using the International Cooperative Ataxia Rating Scale (ICARS). Balance was assessed by dynamic posturography (Biodex, USA) which included: (a) ability to control balance in all directions (overall balance index, OBI), front to back (anterior–posterior index, API) and side-to-side (medio–lateral index, MLI); and (b) the limits of stability (LOS) in all directions. Balance index was considered abnormal if the actual value exceeded the predictive value. Results Impaired balance was found in 80% of patients (all indices in 35%, OBI + API in 25%, only OBI in 15%, and OBI + MLI in 5%). Compared to controls, SCA1 patients had significantly higher balance indices and lower LOS scores. Unlike in controls, the mean value of API was significantly higher than MLI in SCA1. LOS was found to the best predictor of balance abnormality. In patients, all balance indices had significant positive correlations with ICARS, static score of ICARS, body weight, severity and duration of illness, but not with the CAG repeat length. Conclusions Patients with SCA1 had global impairment of balance, with greater instability in anterior–posterior than medio–lateral directions. Apart from severity and duration of illness, body weight was detriment to maintenance of balance in SCA1. This information may be useful in planning balance rehabilitation in SCA.

Selected markers of proliferation and apoptosis in the parathyroid lesions: a spatial visualization and quantification

The aim of the paper was to apply a method for quantitative assessment of proliferation and apoptosis markers, based on their 3D visualization, in cases of parathyroid adenoma and hyperplasia. Material was obtained from 49 patients (32 females and 17 males) with primary hyperparahyroidism. Quantitative immunohistochemistry studies of Ki-67, proliferating cell nuclear antigen (PCNA) and bcl-2 were performed on digital microscopy images with the use of 3D visualization. The use of spatial visualization method allowed us to perform objective quantitative assessment of the studied immunohistochemical markers. The average cell nuclear fraction of Ki67+ was 1.8% in hyperplasia and 1.9% in adenoma cases while 3.5% in the controls. The highest expression of PCNA was found in parathyroid hyperplasia (22.9%) and significantly decreased in adenoma (12.5%) and in the control group (16.8%). The lower expression of bcl-2 in hyperplasia cases (mean area fraction of 0.172 per 1 mum(2), in contrast to 0.643 in adenomas and 0.648 in control) suggested that principal cells can be ready for apoptosis and may confirm the important role of bcl-2 protein in etiopathogenesis of hyperplasia of the parathyroid gland while PCNA might be a useful marker for differentiating adenoma from early hyperplasia in primary hyperparahyroidism cases.

Application of sensory evaluation in food research

Application of sensory evaluation in food research

Assessment of Critical Renal Ischemia With Real-Time Infrared Imaging

Currently visual and tactile clues such as color, mottling, and tissue turgor are used in the operating room for subjective assessments of organ ischemia. Studies have demonstrated that infrared (IR) imaging is a reliable tool to identify perfusion of brain tumors and kidneys during human surgery. Intraoperative IR imaging has the potential for more objective real-time detection and quantitative assessment of organ viability including early ischemia. We hypothesize, by detecting variations of the IR signal, we can assess the degree to which renal surface temperature reflects underlying renal ischemia. To address this hypothesis, IR imaging-derived temperature fluctuations were evaluated during laparotomy in a porcine model (n = 15). These temperature profiles then underwent spectral (frequency) analysis to assess their relationship to well-described oscillations of the microcirculation. An IR camera was positioned 30-60 cm above the exposed kidneys. Images (3-5 mum wavelength) were collected (1.0/s) at baseline, during warm renal ischemia, and during reperfusion. Dominant frequency (DF) of the tissue temperature fluctuations were determined by a Fourier transformation (spectral) analysis. IR images immediately showed which segments of the kidney were ischemic. DF at approximately 0.008 Hz that corresponds to blood flow oscillations was observed in thermal profiles. The oscillations were diminished or disappeared after 25 min of warm ischemia and were recovered with reperfusion in a time-dependent fashion. Oscillations were attenuated substantially in ischemic segments, but not in perfused segments of the kidney. The described oscillations can be measured noninvasively using IR imaging in the operating room, as represented by the DF, and may be an early marker of critical renal ischemia.

Quantitative Analysis of Dynamic Contrast-Enhanced MRI Datasets of the Metacarpophalangeal Joints

In this article, we propose an alternative approach to voxel-by-voxel analysis, which overcomes problems associated with heuristic methods currently used for dynamic contrast-enhanced MRI (DCE-MRI) data assessment. We aim to allow fully automated extraction of various heuristic parameters via robust preprocessing methods and a new technique for classification of temporal patterns of contrast agent uptake, making full use of all available dynamic frames of the datasets. We also demonstrate that application of efficient preprocessing methods permits more accurate analysis of the dynamic data. Ten DCE-MRI datasets enhanced by gadolinium diethylene triamine pentacetic acid were acquired from patients with rheumatoid arthritis using a 1.5-T MRI scanner. Fully automated voxel-by-voxel analysis of DCE-MRI signal intensity curves from 60 temporal slices was performed using a new method. Qualitative evaluation of the degree of inflammation was done via constructing parametric maps and quantitative by computing various heuristics such as maximum rate of enhancement, initial rate of enhancement, and time of onset of enhancement. Quantitative and qualitative evaluation obtained for 10 DCE-MRI datasets is presented. We demonstrate that preprocessing techniques compensate for patient movement, contribute to data fidelity and therefore permit more robust estimation of various heuristics such as maximum rate of enhancement, initial rate of enhancement, and time of onset of enhancement. Automatically generated parametric maps of these heuristics show favorable characteristics, permitting easier differentiation of structures of interest. These results are free from the subjective input and therefore easily reproducible. Furthermore, the proposed classification scheme provides information on the pattern of contrast uptake previously unavailable. Our preliminary results demonstrate the potential of the proposed method for providing objective quantitative and qualitative assessment of DCE-MRI in the metacarpophalangeal joints. Further evaluation within a clinical setting is needed to examine the method's diagnostic utility.

The increasing role of quantification in clinical nuclear cardiology: The Emory approach

Single photon emission computed tomography (SPECT) myocardial perfusion imaging has attained widespread clinical acceptance as a standard of care for patients with known or suspected coronary artery disease. A significant contribution to this success has been the use of computer techniques to provide objective quantitative assessment in interpreting these studies. We have implemented the Emory Cardiac Toolbox (ECTb) as a pipeline to distribute the software tools that we and others have researched, developed, and validated to be clinically useful so that diagnosticians everywhere can benefit from our work. Our experience has demonstrated that integration of all software tools in a common platform is the optimal approach to promote both accuracy and efficiency. Important attributes of the ECTb approach are (1) our extensive number of normal perfusion databases for SPECT and positron emission tomography (PET) studies, each created with at least 150 patients; (2) our use of Fourier analysis of regional thickening to ensure proper temporal resolution and to allow accurate measurement of left ventricular function and dyssynchrony; (3) our development of PET tools to quantify myocardial hibernation and viability; (4) our development of 3-dimensional displays and the use of these displays as a platform for image fusion of perfusion and computed tomography angiography; and (5) the use of expert systems for decision support. ECTb is an important tool for extracting quantitative parameters from all types of cardiac radionuclide distributions. ECTb should continue to play an important role in establishing cardiac SPECT and PET for flow, function, metabolism, and innervation clinical applications.

LETTERS/COMMENTARY

At the “Second International Workshop on Seizure Prediction” held recently in Washington, DC, under the co-sponsorship of NIH/NINDS and the AES, the importance of prospectively comparing the therapeutic efficacy of “closed-” vs. “open-loop” brain electrical stimulation was identified as an important research aim, and the meaning of these terms was briefly debated. Therapies that utilize any type of feedback, including patient seizure diaries, are “closed-loop”. The term “open-loop” was adopted for description of clinical trials with devices lacking automated means for (a) detecting seizures, quantifying their severity, and logging these data; and (b) triggering delivery of therapy based on seizure detections. As currently used, the term “open loop” may create confusion since the therapies to which it is applied rely on patient diary-feedback. The following clarification may be useful: Closed-loop therapy: Any therapy that uses a feedback loop. The feedback may be real-time or delayed (off-line); for both these options, the feedback may be automated or manual, objective or subjective, and may be used to trigger therapy delivery or to adjust parameters or dose. Open-loop therapy: Any therapy that operates without any feedback loop. Recent trials that use automated seizure detection to trigger electrical stimulation directly to the brain (Osorio et al., 2005; Bergey et al., 2006) are examples of automated real-time closed-loop. One of these trials (Osorio et al., 2005) provides real-time automated therapy delivery and objective quantitative assessment of response, while the other (Bergey et al., 2006) provides only automated therapy (as assessment is based on seizure diaries). Vagus nerve stimulation with the neurocybernetic prosthesis (Cyberonics, Houston, TX, U.S.A.), exemplifies two closed-loop modalities: (1) real-time manual closed loop, when the magnet is used to activate the generator in response to an “aura”; and (2) delayed closed loop, when device parameter changes are based upon subjective feedback in the form of seizure diaries. With these definitions in place, the incorrectly stated and irrelevant/futile aim of comparing “open-loop” vs. “closed-loop” therapies should be re-framed. With respect to brain stimulation studies, we offer the following formulation: The aim is to compare efficacy (and adverse events) of therapies that use either continuous, periodic, or random brain electrical stimulation to that of therapies based on contingent stimulation (i.e., in response to) seizure detections. This would be a worthwhile endeavor that should be pursued using objective and quantifiable assessment means such as seizure detection algorithms, instead of patient seizure diaries; diaries are inherently and grossly inaccurate (Blum et al., 1996), provide information only about seizures with clinical manifestations (a small fraction of all recorded seizures) (Osorio et al., 2002), and do not quantify intensity, duration, and extent of spread.

Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury

Prevention of neuron death after peripheral nerve injury is vital to regaining adequate cutaneous innervation density and quality of sensation, and while experimentally proven neuroprotective therapies exist, there lacks suitable clinical outcome measures for translational research. Axotomized dorsal root ganglia (DRG) histologically exhibit volume reduction in proportion to the amount of neuronal death within them. Hence, this study evaluated the validity of using magnetic resonance imaging (MRI) to quantify DRG volume as a proxy measure of cell death. A high-resolution 3D MRI sequence was developed for volumetric quantification of the L4 DRG in the rat sciatic nerve model. An unoperated “control” group ( n = 4), and a “nerve transection” group ( n = 6), 4 weeks after axotomy, were scanned. Accuracy and validity of the technique were evaluated by comparison with morphological quantification of DRG volume and stereological counts of surviving neurons (optical fractionator). The technique was precise (coefficient of variation = 4.3%), highly repeatable (9% variability), and sensitive (mean 15.0% volume reduction in axotomized ganglia detected with statistical significance: p < 0.01). MRI showed strong and highly significant correlation with morphological measures of DRG volume loss ( r = 0.90, p < 0.001), which in turn correlated well with neuron loss ( r = 0.75, p < 0.05). MRI similarly exhibited direct correlation with neuron loss ( r = 0.67, p < 0.05) with consistent agreement. MRI volumetric quantification of DRG is therefore a valid in vivo measure of neuron loss. As a non-invasive, objective measure of neuronal death after nerve trauma this technique has potential as a diagnostic modality and a quantitative tool for clinical studies of neuroprotective agents.

The role of three-dimensional ultrasonography in polycystic ovary syndrome

The 2003 Rotterdam diagnostic criteria for polycystic ovary syndrome (PCOS) support the objective role of ultrasound in defining the appearance of the PCO, but there are significant limitations of these new guidelines from an ultrasound perspective that must be considered. Three-dimensional (3D) ultrasound provides a new method for the objective quantitative assessment of follicle count, ovarian volume, stromal volume and blood flow within the ovary as a whole. Since the introduction of 3D ultrasonography, there have been increasing publications on PCOS, each addressing different areas and reporting different results. This review critically examines these studies in an attempt to clarify the evidence to date and thereby establish the current role of 3D ultrasonography in PCOS.

Quantitative characterization of lung disease

The increase in prevalence, incidence and variety of pulmonary diseases has precipitated the need for more non-invasive quantitative assessment of structure/function relationships in the lung. This need requires concise description not only of lung anatomy but also of associated underlying mechanics of pulmonary function, as well as deviation from normal in specific diseases. This can be facilitated through the use of adaptive deformable surface models of the lung at end inspiratory and expiratory volumes. Lung surface deformation may be used to represent tissue excursion, which can characterize both global and regional lung mechanics. In this paper, we report a method for robust determination and visualization of pulmonary structure and function using clinical CT scans. The method provides both intuitive 3D parametric visualization and objective quantitative assessment of lung structure and associated function, in both normal and pathological cases.

Improvement of cardiac function after haemodialysis. Quantitative evaluation by colour tissue velocity imaging.

Overhydration and accumulation of uraemic toxins may influence the myocardial function in haemodialysis (HD) patients. To evaluate cardiac function and the effects of fluid and solute removal during a single session of HD, colour tissue velocity imaging (TVI) was used. This new technique, which is less load dependent than conventional echocardiography, allows an objective quantitative assessment of myocardial contractility, contraction and relaxation. Conventional echocardiographic and TVI images were recorded before and after a single HD session in 13 clinically stable HD patients (62+/-10 years, six males) and in 13 sex- and age-matched healthy controls. Myocardial tissue velocities (v; cm/s) for isovolumetric contraction (IVC), peak systole (PS), early (E') and late (A') diastolic filling and strain rate (SR) were measured. Left ventricular hypertrophy (LVH) was present in 12 patients. TVI gave additional information in comparison with conventional echocardiography. Before HD, PS (5.0+/-0.8 vs 6.0+/-1.2 cm/s, P<0.05), E' (5.7+/-1.7 vs 7.3+/-2.0 cm/s, P<0.05) and A' (6.6+/-1.7 vs. 8.3+/-2.9 cm/s, P<0.05) velocities were lower in the patients than in the controls, indicating systolic and diastolic dysfunction. The HD session increased IVCv (4.0+/-1.7 to 5.5+/-1.9 cm/s; P<0.001), PSv (5.0+/-0.8 to 5.7+/-0.8 cm/s; P<0.05) and SR (0.7+/-0.2 to 0.9+/-0.2 1/s; P < 0.05) and decreased E/E' (16.7+/-7.7 to 12.2+/-4.0, P<0.05), indicating improved systolic function and decreased LV filling pressure, respectively. Linear regression analysis demonstrated a dependency of systolic contraction (PSv) and contractility (IVCv) upon plasma levels of phosphate (r(2) = 0.70, P<0.005, r(2) = 0.33, P<0.01). Using TVI, HD patients demonstrate myocardial dysfunction, which is found less frequently when using conventional echocardiography. The systolic function seems to be impaired by high plasma levels of phosphate and an increased Ca x P product. One single session of HD improved systolic function as indicated by increases in IVCv, PSv and SR. Further studies are needed to clarify if this effect of HD is due to the acute removal of fluid, the removal of solutes or both.

Urodynamic findings in prostate cancer patients treated with definitive external beam radiotherapy

Purpose: To quantify the effect of radiotherapy (RT) on bladder function, using urodynamic study, in prostate cancer patients undergoing definitive RT. Potential urinary morbidity of RT such as bladder contracture, hematuria, symptomatic cystitis, and urinary incontinence has been a major concern. Up to now, all studies evaluating the effect of RT on urinary function have been qualitative and there has been no objective quantitative assessment. In this prospective study, we used urodynamic study as an objective quantitative tool to examine the nature and degree of change of bladder function caused by RT.

Towards an objective quantitative assessment of daily functioning in migraine: a feasibility study

Migraine is a chronic disabling disorder, with migraine episodes significantly reducing quality of life and leading to impaired functioning (physically, socially, emotionally) both at home and at work. We explored whether ambulatory accelerometry can be used as an objective method to quantify the behavioral aspects of migraine-related disability. Four body mounted uni-axial piezo-resistive accelerometers were used to quantify the time spent in different body postures (lying, sitting, standing), physical activities (walking, cycling) and a general index of body motility during eight migraine attacks and subsequent recovery periods of six patients in their habitual environment. The migraine attacks and recovery periods could be monitored after about 1 h, which was the time required for the investigator to travel to the patient and for the sensors to be attached. In order to quantify the influence of a migraine episode on daily activities, we also performed measurements during a headache-free baseline period of the same patients. Overall, the procedures functioned well, indicating that ambulatory accelerometry measurements before, during and after a migraine attack are feasible to perform. Furthermore, our quantitative data revealed that migraine always influenced behavior by reducing overall body motility and that, dependent upon the severity of the attack, the effectiveness of acute treatment and the time of day, the time spent in various body positions, dynamic activities, and the number of postural transitions were affected. This feasibility study showed that ambulatory accelerometry can provide the objective behavioral effect parameters for the evaluation of migraine and its treatment on daily functioning in the habitual environment of migraine patients.

Effects of Systemically Applied IGF-1 on Motor Nerve Recovery After Peripheral Nerve Transection and Repair in the Rat - A Functional Study.

The trophic effects of systemically applied Rh insulin-like growth factor-1 (rhIGF-1) on peripheral motor nerve regeneration following transection and epineural repair in rats median nerve have been examined. RhIGF-1 (0.5 mg/kg/rat) was administered subcutaneously to the neck region of the repaired side for 14 days post-operation. Motor recovery was tested with the grasping test that is an objective quantitative behavioural assessment of regeneration of the rats median nerve. Muscle twitch tension and muscle weight were measured in the flexor digitorum sublimus muscle. No significant differences between experimental and control animals regarding onset of muscle function, recovery of muscle power, and muscle weight were found. These results demonstrate that subcutaneously applied rhIGF-1 cannot improve functional motor recovery after nerve transection and repair in the rat as has been demonstrated after nerve crushing injury. This is regarded as a consequence of specificity failure during reinnervation, which occurs after nerve transection and repair, whereas after crushing injury specific reinnervation is a common feature.

Projected photovoltaic energy impacts on US CO2 emissions: an integrated energy environmental–economic analysis

The potential role of photovoltaic technologies in reducing carbon dioxide (CO2) emissions in the USA was evaluated using an energy–environment–economic systems model. With a range of assumptions about future scenarios up to 2030, the model results provide an objective quantitative assessment of the prospects for photovoltaics in a competitive market. With the projected improvements in cost and efficiency, photovoltaics will compete favorably as a general source of electricity supply to the grid by about 2010 in southwestern USA. This analysis indicates that photovoltaics has the potential to reach a total installed capacity of 140 GW by the year 2030, and to displace a cumulative 450 million metric tons of carbon emissions from 1995 to 2030. At the projected 2030 capacity, photovoltaics could displace over 64 million metric tons of carbon emissions a year. Under constraints on carbon emissions, photovoltaics becomes more cost effective and would further reduce carbon emissions from the US energy system. © 1997 John Wiley & Sons, Ltd.

Projected photovoltaic energy impacts on US CO2 emissions: an integrated energy environmental–economic analysis

The potential role of photovoltaic technologies in reducing carbon dioxide (CO2) emissions in the USA was evaluated using an energy–environment–economic systems model. With a range of assumptions about future scenarios up to 2030, the model results provide an objective quantitative assessment of the prospects for photovoltaics in a competitive market. With the projected improvements in cost and efficiency, photovoltaics will compete favorably as a general source of electricity supply to the grid by about 2010 in southwestern USA. This analysis indicates that photovoltaics has the potential to reach a total installed capacity of 140 GW by the year 2030, and to displace a cumulative 450 million metric tons of carbon emissions from 1995 to 2030. At the projected 2030 capacity, photovoltaics could displace over 64 million metric tons of carbon emissions a year. Under constraints on carbon emissions, photovoltaics becomes more cost effective and would further reduce carbon emissions from the US energy system. © 1997 John Wiley & Sons, Ltd.

The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation.

Short-chain carboxylic acids (SCCA; C < or = 5; e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which accumulate in the gingival crevice, and exhibit significant biological activity, including the ability to alter gene expression. It has been hypothesized that among the activities of SCCAs are their ability to contribute to gingival inflammation. This concept complements the notion that specific periodontal pathogens are the causative agents of gingival inflammation. To begin testing these 2 hypotheses, we examined the relationship between SCCA concentrations, specific putative periodontal pathogens, and gingival inflammation in medically healthy periodontally diseased subjects. We reasoned that if SCCAs and/or specific periodontal pathogens were causative gingival inflammatory agents, gingival inflammation should increase with increasing concentration of the inflammatory mediator. We also recognized that other clinical variables needed to be controlled for, and an objective quantitative assessment of gingival inflammation used. To accomplish these tasks, sites within subjects were stratified by location and pocket depth, and the following quantified: bacterial presence; SCCA concentration; and gingival inflammation. The results indicated that gingival inflammation directly and significantly correlated with SCCA concentrations in the maxillary and mandibular molars, incisors and canines (all r > or = 0.47; all p < or = 0.015; too few bicuspids were available for complete analysis). The relationship between gingival inflammation and SCCA concentration was best described by a natural log relationship. Gingival inflammation did not, however, correlate positively with either the total number of specific putative periodontal pathogens, or the sum of subsets of these pathogens (-0.31 < or = r < or = 0.39; 0.08 < or = p < or = 0.75) for any of the locations. Finally, the SCCA concentration did not correlate with the level of individual or groups of pathogens. These data, together with historical work and other preliminary data, support the hypothesis that SCCA, rather than specific putative periodontal pathogens, may be a causative agent in gingival inflammation. This work may, in part, begin to explain the apparent lack of a direct relationship between current gingival inflammation and the prediction of bacterially mediated periodontal attachment loss.