Compositional modelling of immune response and virus transmission dynamics.

Transmission models for infectious diseases are typically formulated in terms of dynamics between individuals or groups with processes such as disease progression or recovery for each individual captured phenomenologically, without reference to underlying biological processes. Furthermore, the construction of these models is often monolithic: they do not allow one to readily modify the processes involved or include the new ones, or to combine models at different scales. We show how to construct a simple model of immune response to a respiratory virus and a model of transmission using an easily modifiable set of rules allowing further refining and merging the two models together. The immune response model reproduces the expected response curve of PCR testing for COVID-19 and implies a long-tailed distribution of infectiousness reflective of individual heterogeneity. This immune response model, when combined with a transmission model, reproduces the previously reported shift in the population distribution of viral loads along an epidemic trajectory. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Rule-based epidemic models.

Rule-based models generalise reaction-based models with reagents that have internal state and may be bound together to form complexes, as in chemistry. An important class of system that would be intractable if expressed as reactions or ordinary differential equations can be efficiently simulated when expressed as rules. In this paper we demonstrate the utility of the rule-based approach for epidemiological modelling presenting a suite of seven models illustrating the spread of infectious disease under different scenarios: wearing masks, infection via fomites and prevention by hand-washing, the concept of vector-borne diseases, testing and contact tracing interventions, disease propagation within motif-structured populations with shared environments such as schools, and superspreading events. Rule-based models allow to combine transparent modelling approach with scalability and compositionality and therefore can facilitate the study of aspects of infectious disease propagation in a richer context than would otherwise be feasible.

Acinic cell carcinoma of the parotid gland: from pathogenesis to management: a literature review.

PURPOSE: Acinic cell carcinoma (ACCs) is uncommon malignant epithelial neoplasm of the salivary glands; the most common presentation is a well-defined painless solid mass. Diagnosis of ACCs is frequently complicated, due to its similarity with benign tumors. METHODS: A review of the literature available on ACCs was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. RESULTS: There are no clear characteristics of ACCs found on CT, MRI and ultrasound imaging. The management of the ACC, a rare malignancy of the parotid gland, is often difficult and controversial. Radical surgery is the best treatment option. The role of radiotherapy remains controversial: the precise indications and oncologic effects of adjuvant radiotherapy in ACC of the parotid gland are not well known. There is insufficient literature regarding the chemotherapy for metastatic ACC. CONCLUSION: Knowledge about ACC, a rare malignancy of parotid gland, has changed over the past few decades. More clinical randomized works would be needed, both to assess the real effectiveness of radio and chemotherapy and to have an unanimous consensus about their indications.

Cholesteatoma vs granulation tissue: a differential diagnosis by DWI-MRI apparent diffusion coefficient.

PURPOSE: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. METHODS: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. RESULTS: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10- 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10- 3 mm2/s) group (p < 2.2 × 10- 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10- 3 mm2/s. CONCLUSIONS: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.

Recurrent epistaxis following stabbing headache responsive to acetazolamide.

The co-occurrence of epistaxis and headache is not uncommon in migraine patients, although only few case reports have been published. A trigeminovascular activation may be causally involved although the exact mechanisms linking epistaxis and migraine remain unclear. Significant dural sinus stenosis may sustain or worsen an increased cerebral venous pressure and is considered a radiological predictor of idiopathic intracranial hypertension. We report a 49-year-old female patient with chronic migraine associated to stabbing headache-like attacks followed by epistaxis and by the resolution or the significant improvement of pain. As she also reported adjunctive symptoms suggestive of raised intracranial pressure and showed a bilateral narrowing of transverse sinuses at MR-venography, a possible intracranial hypertension was hypothesized despite the lack of papilledema. Acetazolamide 250 mg twice/day was added to therapy and the patient reported sudden reduction of headache severity and frequency and complete resolution of both the stabbing pain and the recurrent epistaxis, maintained for 5 months. At treatment discontinuation she complained the worsening of migraine headache and the reoccurrence of the superimposed stabbing pain followed by epistaxis. The mechanism linking the sequential occurrence of painful stabs, epistaxis and relief from pain with raised intracranial pressure in our patients remains unclear. We speculate that the sudden reopening of collapsed collateral veins of the anterior venous circle, possibly prompted by periodic waves of central venous hypertension coupled with intracranial hypertensive peaks, could explain the unusual strict time succession of painful stabs, epistaxis, and subsequent resolution of pain.

Assessing the ecological quality status of the highly polluted Bagnoli area (Tyrrhenian Sea, Italy) using foraminiferal eDNA metabarcoding.

Morphology-based benthic foraminifera indices are increasingly used worldwide for biomonitoring the ecological quality of marine sediments. The recent development of foraminiferal eDNA metabarcoding offers a reliable, time-, and cost-effective alternative to morphology-based foraminiferal biomonitoring. However, the practical applications of these new tools are still highly limited. In the present study, we evaluate the response of benthic foraminifera and define the ecological quality status (EcoQS) in the Bagnoli area (Tyrrhenian Sea, Italy) based on a traditional morphology-based approach and eDNA metabarcoding. The geochemical data show that several sites in front of the former industrial plant contain higher concentrations of potentially toxic elements than the effect range median and are characterized by the highest total organic carbon (TOC) content, whereas the distantly located sites can be considered relatively low- to unpolluted. Significant differences (i.e., diversity and assemblage composition) in both morphological and molecular datasets were found between the relatively low- to unpolluted and the most polluted areas. Similarly, the selected ecological indices of both morphological and molecular datasets strikingly and congruently resulted in a clear separation following the environmental stress gradient. The molecular indices (i.e., g-exp(H'bc), g-Foram AMBI, and g-Foram AMBI-MOTUs) reliably identified poor-to-bad EcoQS in the polluted area in front of the former industrial plant. On the other hand, the Foram-AMBI based on morphology well identified an overall trend but seemed to overestimate the EcoQS if the traditional class boundaries were considered. The congruent and complementary trends between morphological and metabarcoding data observed in the case of the Bagnoli site further support the application of foraminiferal metabarcoding in routine biomonitoring to assess the environmental impacts of heavily polluted marine areas.

Evaluation of Discomfort in Nasopharyngeal Swab Specimen Collection for SARS-CoV-2 Diagnosis.

BACKGROUND: The rapid spread of COVID-19 worldwide has impo-sed the need to identify a test that quickly recognizes affected subjects, both symptomatic and asymptomatic. The most reliable option has been proven to be the RT-PCR, which allows to detect virus RNA on a specimen from a high viral load site, such as nasopharynx. Nasopha-ryngeal sample collection is possible by means of a nasopharyngeal swab (NPS) and is a practical and relatively non-invasive technique, but rather bothersome for the recipient. AIM: The aim of the present study is to evaluate the discomfort evoked during NPS. MATERIALS AND METHODS: We surveyed 429 patients receiving NPS before hospitalization or other procedures non related to COVID-19. For each one we noted the discomfort level felt during the swab using a 11-point numeric rating scale (NRS) for pain and the total time needed for the procedure to be taken. Sex, age, smoking status and positive history of previous swab have been taken into account. RESULTS: We found that, among the variables, sex had a statistically significant impact on the perceived discomfort of nasal swab, with females experiencing slightly more discomfort. CONCLUSIONS: NPS is largely a none-to-minimum discomfort in-ducing procedure. The differences in perceived discomfort could be explained based on anatomical features, and should remark the need for a tailored and anatomy-oriented approach in each patient.

Pleomorphic Adenoma of the Parotid Gland and Ipsilateral Thyroid Incidentaloma: Report of A Rare Case With Review of Literature.

BACKGROUND: Pleomorphic adenomas are benign tumors of the salivary glands that mainly affect the lower pole of the superficial lobe of the parotid gland. The term "pleomorphic" refers to the epithelial and connective origin of the mass. The clinical presentation is typically that of asymptomatic swelling which increases in volume. Therapy consists in surgical removal of the tumor mass by parotidectomy with nerve preservation. CASE DETAILS: This clinical case describes an interesting case of pleomorphic adenoma of the parotid gland in a 62-year-old patient. The patient presented with a long history of an asymptomatic mildly worsening swelling of the left parotid region. The peculiarity of the clinical case is the dimension of the adenoma (9x5x9 cm) and the presence of a thyroid incidentaloma (TI), consisting of a thyroid multinodular goiter composed of nodules, the largest of which measured 8 cm in diameter. This mass dislocated the laryngotracheal axis, compressed the larynx and caused the reduction of the respiratory space, making orotracheal intubation difficult and determining the need to perform a tracheotomy. CONCLUSION: Benign pleomorphic adenomas can potentially reach large sizes if untreated. Socio-economic problems may be the reason for late diagnosis.

Pharmacological, Surgical and Diagnostic Innovations in Meniere's Disease: A Review.

PURPOSE: To investigate literature about pharmacological, surgical, and diagnostic innovations for Meniere's Disease (MD). SUMMARY: Meniere's disease is an inner ear disorder characterized by the presence of endolymphatic hydrops in the inner ear and symptomatology of recurrent and debilitating vertigo attacks, tinnitus, aural fullness, and fluctuating sensorineural hearing loss. Although many therapeutic options for MD have been proposed during years, no consensus has been reached by the scientific community. In the last decade, many therapeutic options have been proposed, as intratympanic steroid, intratympanic gentamicin, and intravenous glycerol. Recently, the role of the antisecretory factor in the diet of MD patients have been investigated. Surgery is recommended for intractable MD; some authors proposed new approaches including transcanal endoscopic infracochlear vestibular neurectomy, new marsupiliazation technique in sac surgery, and tenotomy of the stapedius and tensor tympani muscles.

Drug-Induced Sleep Endoscopy (DISE) with Simulation Bite to Predict the Success of Oral Appliance Therapy in Treating Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS).

STUDY OBJECTIVES: Oral appliances have gained their place in the treatment of obstructive sleep apnea (OSA) where custom-made titratable mandibular advancement devices (MAD) have become the oral appliance of choice. This study aimed to asses the value of the drug-induced sleep endoscopy (DISE) using a MAD in the prediction of treatment outcome for OSAHS. METHODS: This is a prospective, single-center cohort study that enrolled sixty-six consecutive patients with diagnosed OSA (5 events/h < apnea-hypopnea index (AHI) < 50 events/h) to be treated with a custom-made titratable MAD. The patients were evaluated polysomnographically with the MAD in situ after the adaptation and titration period of 3 months. The associations between findings during DISE and treatment outcome were assessed. RESULTS: The subjects showed a wide range of severity of OSAHS pre-treatment: median AHI was 43.10 with a range from 20.13 to 66.07. The simulation bite was associated with a significant increase in cross-sectional area at level of the velopharynx, tongue base and epiglottis. MAD treatment response in the studied population was 91%, with a mean AHI improving from 43.10 to 12.93. CONCLUSIONS: Drug-induced sleep endoscopy with simulation bite is an acceptably reproducible technique for determining the sites of obstruction in OSAHS subjects; it thus offers possibilities as a prognostic indicator for treatment with MAD.

Dietary Restriction for The Treatment of Meniere's Disease.

Meniere's disease (MD) is an idiopathic inner ear disorder characterized by spontaneous recurrent vertigo, fluctuating sensorineural hearing loss (SNHL), aural fullness and tinnitus. Endolymphatic hydrops (EH) of the inner ear is currently considered the pathophysiological mechanisms that underlies typical symptoms of MD. MD diagnosis is based on the criteria of the Baràny Society. There are many therapeutic options for MD, but none is considered effective by the scientific community. The first-line treatment commonly includes dietary modification, as low salt diet and reduction of alcohol and caffeine daily intake. Although some studies showed a positive effect of these dietary restrictions, even in the prevention of recurrences, currently there is no uniform consensus on their usefulness. New dietary approach, such SPC-flakes, are being evaluated: further assessments will be needed to validate their use in clinical practice.

Oncocytic cyst of the larynx: an unusual occurrence.

Oncocytic cysts of the larynx are rare benign, slow growing lesions that are lined predominantly or exclusively by oncocytes, the cytoplasm of which contains a considerable number of hypertrophied mitochondria, which accounts for their eosinophilia and swollen appearance. The oncocytic change is a phenomenon of metaplasia which occurs frequently in epithelial endocrine cells with high metabolic activity and it is also associated with inflammation, degenerative process or cellular ageing. In the larynx, oncocytic metaplasia is very uncommon, but it is occasionally seen in the lining of laryngeal cysts, which are found most commonly in the ventricles or in the false vocal cords, where seromucinous glands are more abundant. Oncocytic cysts typically occur in the elderly and are usually solitary, with involvement of an isolated site, whereas diffuse involvement with multiple cysts is extremely rare. Hoarseness is the most common presenting symptom, while pain, stridor or laryngeal obstruction are unusual complaints. Management of these lesions is conservative and consists of local excision, endoscopic removal being the treatment of choice. Although oncocytic cysts are benign lesions, follow-up is recommended, as recurrence is possible, especially in the case of patients with multiple involvement, since they may show a tendency to develop new cysts. To date, approximately 150 cases of laryngeal oncocytic cysts have been published. Herein, a very unusual case is presented occurring in a 43-year-old male patient, therefore, "epidemiologically" atypical for developing oncocytic lesions. Causes of oncocytic changes and pathogenesis of laryngeal cysts are discussed.

Stabilometric findings in patients affected by organic dysphonia before and after phonomicrosurgery.

The purpose of this study is to understand if there is any alteration in the posture of patients affected by organic dysphonia and describe possible postural modifications after phonomicrosurgery on the vocal folds. Forty subjects (22 males, 18 females; mean age 32.6 ± 7.5 years) suffering from organic dysphonia (15 cases of polyps, 11 submucosal retention cysts, 10 bilateral fibrous vocal fold nodules and 4 bilateral Reinke's oedema) were examined by open-eye and closed-eye posturography while breathing spontaneously before surgery, 24 hours after surgery and after 6 months. The variables taken into account were: the coordinates of the centre of pressure on both frontal and sagittal planes, length and surface of the track, mean velocity of the oscillations and relative standard deviations, spectral analysis of oscillation frequency, statokinesigram and stabilogram values. No characteristic pathological pattern was seen in basal stabilometry in any of the subgroups (polyps, cysts, Reinke's oedema). Only the subgroup of patients with fibrous vocal fold nodules (8/10; 80%) showed a slight forward shift from the centre of gravity when analysed in both open-eye and closed-eye posturography. A comparison performed within the same subgroup using open-eye and closed-eye posturography before and after surgery revealed no significant difference in any of the parameters being studied. The use of static stabilometry in this study demonstrates the absence of characteristic postural alterations in patients affected by organic dysphonia and also excludes that simple removal of the vocal fold lesion can change posture.

Otorhinolaryngology-related tuberculosis.

Data from personal case histories, from 1984 to 2000 inclusive, are reported in order to contribute to a better understanding of some of the clinical and epidemiological ENT associated TB aspects. Analysis of these data shows that: (1) Like the pulmonary form, ENT localizations are increasing due to the traditional risk factors (immigration, poverty, immunodeficiency, drug addiction). (2) They are generally clinically primitive forms (which are found in extrapulmonary regions as the first expression of tubercular disease) and typically affect young people with a slight prevalence among females. Lymph gland localizations are the most frequent.

Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors' mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with advanced resistant Hodgkin's disease and non-Hodgkin's lymphoma. PATIENTS AND METHODS: Fifteen patients with Hodgkin's disease (n = 10) and non-Hodgkin's lymphoma (n = 5) were studied. All patients received cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m(2) with cyclophosphamide 300 mg/m(2) daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed >/= grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection. CONCLUSION: Fludarabine/cyclophosphamide was well tolerated and allowed consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.

Benign paroxysmal positional vertigo: a study of two manoeuvres with and without betahistine.

Efficacy of the liberatory manoeuvre and of gradual otolitis dispersion technique, with or without associated drug therapy, have been compared. Included in this prospective study were 103 patients with benign paroxysmal positional vertigo seen in the Outpatient Department. Patients were classified into 4 groups according to treatment: Liberatory Manoeuvre according to methods described by Semont et al., with and without betahistine, Gradual Otolitis Dispersion Technique according to Brandt and Daroff, with and without betahistine. Evaluation was performed at baseline and at 3, 7, 14, 30, 60 and 90 days after start of treatment. Response to treatment was evaluated using criteria of Epley. At day 14, liberatory manoeuvre-betahistine and Brandt and Daroff-betahistine groups did significantly better than liberatory manoeuvre and Brandt and Daroff groups (p < 0.05). Improvement reached at day 30 was: 100% in liberatory manoeuvre-betahistine group; 96.30% (p > 0.05) in Brandt and Daroff-betahistine group; these results were significantly better (p < 0.05) than those of liberatory manoeuvre (54.17%) and Brandt and Daroff (25%) groups. As far as concerns differences between disease onset and start of therapy (less and more than 2 weeks), and age (< or =60 years and > or =60 years), response to treatment was similar. In conclusion, both liberatory manoeuvre and Brandt and Daroff, when associated with betahistine, were significantly more effective than manoeuvres alone (p < 0.05). Improvement in liberatory manoeuvre-betahistine group, in the initial phase, was greater that in Brandt and Daroff-betahistine group, albeit, differences were not significant (p > 0.05). Age-related effects of manoeuvres were compared in 71 patients < 60 years and 32 patients > or =60 years, showing a similar improvement rate at the end of the investigation in both groups. In our opinion, liberatory manoeuvre and Brandt and Daroff associated with betahistamine produces faster recovery compared to liberatory manoeuvre and Brandt and Daroff alone. Nevertheless, 3 months after onset of treatment, all patients showed complete recovery due to spontaneous evolution of paroxysmal positional vertigo, in other words, treatment does not appear to influence the final improvement rate and its role should be accepted as a significant reduction in persistence of symptoms.

Cytogenetic response to autografting in chronic myelogenous leukemia correlates with the amount of BCR-ABL positive cells in the graft.

OBJECTIVE: An important step in successful autografting of patients with chronic myelogenous leukemia is the delivery of a leukemia-free graft. We conducted this study to determine whether the cytogenetic response after autografting was correlated with the number of BCR ABL-positive cells present within the stem cell grafts. MATERIALS AND METHODS: By BCR-ABL mRNA quantification, we studied the serial pheresis products from 40 Philadelphia (Ph)-positive patients who received ICE/mini-ICE mobilization therapy and underwent autologous stem cell transplantation. We correlated the residual disease within the graft reinfused with the cytogenetic response following transplantation, taking into consideration those responses that lasted 12 months or more. RESULTS: Thirty-two patients received a graft with 0-35% Ph-metaphases and 19 received a graft with BCR-ABL/ABL ratio < or =0.01. After a median of 27 months (range, 12-50) from transplant, 18 patients achieved complete or major cytogenetic response lasting at least 12 months, and 14 of them (78%) received a graft with BCR-ABL/ABL ratio < or =0.01 (range, 0.0003-0.01). Twenty-two patients experienced short-lived responses or had >35% Ph-positive cells in the marrow after transplant, but only 5 of them (23%) had a graft with BCR-ABL/ABL ratio < or =0.01 (range, 0.001-0.01). Therefore, we found a strong association between a BCR-ABL/ABL ratio less than or =0.01 and the achievement of complete or major cytogenetic remission after autografting (chi(2) test, p = 0.0001). Patients reinfused with grafts contaminated at low levels with leukemic cells also showed a longer duration of the response (log-rank test, p = 0.0009). Eleven patients were reinfused with the lowest level of contaminated stem cell collections, according to the BCR-ABL/ABL ratio. None of these patients experienced prolonged neutropenia or thrombocytopenia following stem cell reinfusion and nine of them had long-lasting complete or major cytogenetic responses after transplant. CONCLUSION: This study demonstrates that the number of BCR-ABL positive cells present in a stem cell graft is an important predictive factor for the achievement and the duration of cytogenetic response after autografting. [corrected]

Diffusion weighted MR imaging of primary and recurrent middle ear cholesteatoma: an assessment by readers with different expertise.

INTRODUCTION AND PURPOSE: Diffusion weighted imaging (DWI) has been proven to be valuable in the diagnosis of middle ear cholesteatoma. The aims of our study were to evaluate the advantage of multi-shot turbo spin echo (MSh TSE) DWI compared to single-shot echo-planar (SSh EPI) DWI for the diagnosis of cholesteatoma. MATERIAL AND METHODS: Thirty-two patients with clinical suspicion of unilateral cholesteatoma underwent preoperative MRI (1.5T) with SSh EPI and MSh TSE. Images were separately analyzed by 4 readers with different expertise to confirm the presence of cholesteatoma. Sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) were assessed for each observer and interrater agreement was assessed using kappa statistics. Diagnosis was obtained at surgery. RESULTS: Overall MSh TSE showed higher diagnostic accuracy and lower negative predictive value (NPV) compared to conventional SSh EPI. Interreader agreement between the observers revealed the superiority of MSh TSE compared to SSh EPI. Interrater agreement among all the four observers was higher by using MSh TSE compared to SSh EPI. CONCLUSION: Our findings suggest that MSh TSE DWI has higher sensitivity for detection of cholesteatoma and lower probability of misdiagnosis. MSh TSE DWI is useful in guiding less experienced observers to the diagnosis.

Disposition of pirprofen, a new anti-inflammatory drug.

Plasma and urine concentrations of 2-(3-chloro-4[3-pyrrolinyl]phenyl) propionic acid, pirprofen, a new nonsteroidal anti-inflammatory compound, are described for normal male volunteers receiving one or more doses of the drug. Orally administered pirprofen is rapidly and almost completely absorbed from the gastrointestinal tract, resulting in maximum plasma levels in 1 to 2 hr. Mean peak levels are 23 microng/ml after an oral pirprofen dose of 200 mg; lower doses given proportionally lower levels. Administration 1 hr after a meal slightly delays the peak plasma level, but the extent of absorption is not affected significantly. Administration of pirprofen, 150 mg, 4 times daily, or 200 mg, 3 times daily, results in nearly identical plasma levels at steady-state. Pirprofen has an apparent elimination half-life of about 7 hr. The results obtained from a 200-mg pirprofen-14C dose indicate that excretion of the drug occurs primarily by the renal route in the form of metabolites and is essentially complete within 24 hr. In urine, less than 5% of the administered dose is accounted for as unchanged drug.