Pathways to renal biopsy and diagnosis among patients with ANCA small-vessel vasculitis.

OBJECTIVES: Antineutrophil cytoplasmic antibody small-vessel vasculitis (ANCA-SVV) is an autoimmune systemic process increasingly recogniSed since the advent of antibody testing for the disease. Prompt diagnosis and institution of immunosuppressive therapy has been shown to improve patient outcome. The goal of this study was to better understand how patients navigate the health care system from symptom presentation to biopsy diagnosis, and to study the effects of prompt versus delayed diagnosis. METHODS: Disease symptoms and number of physicians seen prior to renal biopsy were assessed for 127 ANCA-SVV patients. Direct, delayed, and quest pathways to diagnosis and treatment of vasculitis were defined for both patients and providers. Kruskal-Wallis and Fisher exact tests were used to evaluate continual measures and compare categorical variables across pathways. RESULTS: Among patients who sought direct care, physician delay in referral to a nephrologist was common (49/127, 71%, p=0.0023). Patients who delayed seeking care also experienced a delayed diagnosis 57% of the time (p=0.0023). Patients presenting with prodromal flu or upper respiratory involvement were more likely to have a delay/quest patient pathway (56% and 55%, respectively) than a direct patient pathway (44%, p=0.033 and 45%, p=0.019, respectively). There was a trend for patients with more severe loss of renal function to have a more direct referral to a nephrologist. CONCLUSIONS: Delay in diagnosis of ANCA SVV may be due to lack of or non-specific symptoms, especially in patients who present with non-renal manifestations of disease. Better algorithms are needed to identify extra-renal manifestations, expedite diagnosis and improve patient outcomes.

Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations.

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.

Mapping of myeloperoxidase epitopes recognized by MPO-ANCA using human-mouse MPO chimers.

Myeloperoxidase (MPO) is one of the major target antigens of antineutrophil cytoplasmic autoantibodies (ANCA) found in patients with small-vessel vasculitis and pauci-immune necrotizing glomerulonephritis. To date, the target epitopes of MPO-ANCA remain poorly defined. Human MPO-ANCA do not typically bind mouse MPO. We utilized the differences between human and mouse MPO to identify the target regions of MPO-ANCA. We generated five chimeric MPO molecules in which we replaced different segments of the human or mouse molecules with their homologous counterpart from the other species. Of serum samples from 28 patients screened for this study, 43 samples from 14 patients with MPO-ANCA-associated vasculitis were tested against recombinant human and mouse MPO and the panel of chimeric molecules. Sera from 64 and 71% of patients bound to the carboxy-terminus of the heavy chain, in the regions of amino acids 517-667 or 668-745, respectively. No patient serum bound the MPO light chain or the amino-terminus of the heavy chain. All sera bound to only one or two regions of MPO. Although the pattern of MPO-ANCA binding changed over time (4-27 months) in 6 of 10 patients with several serum samples, such changes were infrequent. Other target regions of MPO-ANCA may not have been detected due to conformational differences between the native and recombinant forms of MPO. MPO-ANCA do not target a single epitope, but rather a small number of regions of MPO, primarily in the carboxy-terminus of the heavy chain.

Difference in antigenic determinant profiles between human and rat myeloperoxidase.

We tested whether rat and human MPO have similar antigenic determinants using 36 human MPO-ANCA positive sera, one mouse anti-rat MPO and four mouse anti-human MPO monoclonal reagents. Purified rat and human MPO were used in ELISA, with or without crossinhibition by preincubation with human MPO or irrelevant antigen in the liquid phase. Only one human MPO ANCA positive serum exhibited significant binding in rat MPO ELISA. This binding was poorly inhibited by preincubation with human MPO in the liquid phase, but was conserved after adsorption of non specific anti-rat activity in a chromatography column. Three mouse anti-human MPO IgG monoclonal antibodies did not recognize rat MPO. Only one mouse anti-human MPO IgA monoclonal antibody bound to rat MPO. This binding was poorly inhibited by preincubation with human MPO (35% at 2 micro g/ml). Conversely, the mouse anti-rat MPO monoclonal did not bind human MPO. We have concluded that: (1) Most human MPO-ANCA recognize antigenic determinants on human MPO which are absent on rat MPO. Therefore, human auto-antibodies bind to epitopes which recently appeared after species evolution; (2) Inversely, the mouse anti-rat MPO monoclonal do not bind human MPO. Therefore, rat MPO epitopes have been altered during species evolution; (3) Mice injected with human MPO preferentially develop antibodies against xeno-epitopes which are not present in rodents. Therefore, human MPO may not be the best antigen to raise ANCA in animal models and (4) A comparison of the amino acid sequences of rat and human MPO may help elucidate the major antigenic epitopes.

Restriction in V kappa gene use and antigen selection in anti-myeloperoxidase response in mice.

Anti-neutrophil cytoplasmic Abs, directed primarily toward myeloperoxidase (MPO) and proteinase 3, are detected in the majority of patients with distinct forms of small vessel vasculitides and pauci-immune necrotizing glomerulonephritis. However, the origin of these autoantibodies remains unknown. We studied the V region gene use in murine anti-MPO Abs derived from Spontaneous Crescentic Glomerulonephritis/Kinjoh mice. A total of 13 anti-MPO-producing hybridomas were generated from four unimmunized mice. Ten of the 13 hybridomas (corresponding to 3 of 4 clones) expressed Vkappa1C but differed in their use of VH genes. The remaining three hybridomas expressed a Vkappa5 gene. Anti-MPO hybridomas from individual mice were derived from single clones as deduced by sequence similarity and splice-site identity. We found a statistically significant bias of amino acid replacement mutations to the complementarity-determining regions (CDR) in the Vkappa1C-expressing hybridomas. Intriguingly, all 10 Vkappa1C hybridomas share a lysine to glutamate mutation in the CDR1. To determine the effects of somatic V gene mutations on binding to MPO, we generated an anti-MPO Ab with an unmutated Vkappa1C L chain and compared its ability to bind MPO with its mutated counterpart. The mutated hybridoma-derived Ab has a 4.75-fold higher avidity for MPO than the unmutated Ab. These results suggest that: 1) the L chain plays a dominant role in determining Ab specificity to MPO, 2) the anti-MPO Ab response is oligoclonal, consistent with Ag selection, and 3) MPO is a driving Ag in the murine anti-MPO Ab response.

False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: a source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies.

Anti-myeloperoxidase antibodies (anti-MPO) are a major type of anti-neutrophil cytoplasmic antibody (ANCA). While evaluating anti-MPO monoclonal antibodies from SCG/Kj mice, we observed several hybridomas that appeared to react with both MPO and DNA. Sera from some patients with systemic lupus erythematosus (SLE) also react with MPO and DNA. We hypothesized that the MPO binding activity is a false-positive result due to the binding of DNA, contained within the antigen binding site of anti-DNA antibodies, to the cationic MPO. Antibodies from tissue culture supernatants from 'dual reactive' hybridomas were purified under high-salt conditions (3 M NaCl) to remove any antigen bound to antibody. The MPO and DNA binding activity were measured by ELISA. The MPO binding activity was completely abrogated while the DNA binding activity remained. The MPO binding activity was restored, in a dose-dependent manner, by the addition of increasing amount of calf-thymus DNA (CT-DNA) to the purified antibody. Sera from six patients with SLE that reacted with both MPO and DNA were treated with DNase and showed a decrease in MPO binding activity compared with untreated samples. MPO binding activity was observed when CT-DNA was added to sera from SLE patients that initially reacted with DNA but not with MPO. These results suggest that the DNA contained within the antigen binding site of anti-DNA antibodies could bind to the highly cationic MPO used as substrate antigen in immunoassays, resulting in a false-positive test.

ANCA glomerulonephritis and vasculitis: a Chapel Hill perspective.

Microscopic polyangiitis, Wegener's granulomatosis, Churg-Strauss syndrome, and pauci-immune necrotizing glomerulonephritis share pathogenic, pathological, and clinical features. They all involve capillaries, venules, arterioles, and small arteries. Approximately 90% of patients have autoantibodies either to myeloperoxidase (MPO-ANCA) or to proteinase 3 (PR3-ANCA). The clinical manifestations of ANCA-small vessel vasculitis are protean. These can be limited to the kidney alone, or may involve the upper respiratory tract, the lungs, the skin, or a number of other organs in various combinations. The characteristic feature of the glomerular lesion is a focal necrotizing glomerulonephritis associated with crescent formation and little or no glomerular staining for immunoglobulin by immunofluorescence microscopy. The renal manifestations can present as a rapidly progressive glomerulonephritis or that of a more indolent, remitting, and relapsing course that leads to substantial glomerulosclerosis. The two main prognostic markers of the long-term outcome are the presence of pulmonary hemorrhage (which accounts for at least half of all deaths) and the entry serum creatinine. The higher the entry serum creatinine, the higher the risk of developing end-stage renal disease. The treatment of ANCA-small vessel vasculitis and glomerulonephritis rests primarily on the use of induction high-dose corticosteroids and cyclophosphamide. Patients with pulmonary hemorrhage also benefit from plasmapheresis. With the use of an alkylating agent, the rate of remission is of the order of 75%, but relapses occur in about 30% of patients who achieve a remission, and in about 17% of patients after renal transplantation. Despite the improved outcome of patients with ANCA vasculitis in the recent decade, their long-term prognosis continues to be primarily determined by a rapid diagnosis, and the prompt institution of therapy.

Recurrent ANCA-associated small vessel vasculitis after transplantation: A pooled analysis.

BACKGROUND: Recurrent antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis (ANCA-SVV) after renal transplantation has been described in case series. However, general information regarding the frequency, character, and predictors of recurrent disease after transplantation is currently lacking. We considered the rate of relapse, whether a positive ANCA at the time of transplantation predicted relapse, and whether cyclosporine A prevented recurrent disease. METHODS: We performed a pooled analysis of published data, added to the experience at the Universities of North Carolina (14 patients) and Lund, Sweden (11 patients). To avoid reporting bias, only case series were included for analysis. Subgroup analysis was performed by disease category (Wegener's granulomatosis, microscopic polyangiitis, or necrotizing crescentic glomerulonephritis) and ANCA staining pattern. RESULTS: ANCA-SVV recurred in 17.3% of all patients (N = 127), in 20% of cyclosporine A-treated patients (N = 85), and in 25.6% of patients with circulating ANCA at the time of transplantation (N = 39). There was no statistically significant difference in the relapse rate between patients treated and those not treated with cyclosporine A (P = 0.45), between those with and without circulating ANCA at the time of transplant (P = 0.75), or between patients with Wegener's granulomatosis and those with microscopic polyangiitis or necrotizing crescentic glomerulonephritis alone (P = 0.62). CONCLUSION: There is a substantial relapse rate in the ANCA-SVV population. Therapy with cyclosporine A does not protect against recurrent ANCA-SVV, and the presence of a positive ANCA at the time of transplantation does not preclude transplantation. These conclusions must be substantiated with a prospective study of renal transplantation in patients with ANCA-SVV so as to optimize their management.

Mycophenolate mofetil therapy in lupus nephritis: clinical observations.

Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens. This study reports on the clinical experiences at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis. Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included. During combined MMF/prednisone therapy, serum creatinine values remained normal or declined from elevated values: mean change in serum creatinine was -0.26+/-0.46 microM/L, P = 0.039. Proteinuria significantly decreased: mean change in urine protein-to-creatinine ratios was -2.53+/-3.76, P = 0.039. Decreased serum complement component C3 and elevated anti-double-stranded DNA antibody levels at baseline improved in some, but not all, patients. The mean initial dose of MMF was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated with severe leukopenia (n = 1), asymptomatic leukopenia (n = 2), nausea/ diarrhea (n = 2), thinning of scalp hair (n = 1), pancreatitis (n = 1), and pneumonia without leukopenia (n = 1). Recurrence of the pancreatitis led to discontinuation of MMF in this patient; all other adverse events resolved with dose reduction. It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus. Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis.

Maternal identification: a description of the process in real time.

This research, using the method of microanalysis, explores the to-and-fro activity of the self- and object representational world of mothers as they observe their children. Under examination is a "moment" usually lasting not more than 5-20 seconds that was selected by the mother as outstanding to her during the time she was observing her child. A microanalytic interview technique was developed in which the mother is asked about everything she experienced about "the moment," including what she was feeling, imagining, doing, perceiving, and remembering. At brief intervals she was asked to indicate on a scale where--on herself or her child--her experience was centered. These data were organized in terms of tracking the locus of the mother's perspective: from dwelling in her own mind (self-representation) to inhabiting that of her child (object representation). Results indicate that these representational shifts occurred frequently, usually every one to three seconds, and that there were significant individual differences among the mothers.

Qualitative light-scattering angular correlations of conglomerate particles.

The scattering phase functions of micrometer-sized glycerol droplets containing spherical latex inclusions undergo random fluctuations with time. We measure scattering intensities in the near-forward and near-backward scattering directions and find them to have strong positive correlations during some time periods and strong negative correlations during other time periods. The characteristic time constants of these correlations are of the order of seconds. We calculate scattering correlations from two types of scattering system. Correlations from a two-sphere system generally are positive, whereas correlations from a sphere containing a single spherical inclusion may be both positive and negative. Calculations of correlations from our experimental data are consistent with diffusion of inclusions within the host droplet, rather than interference effects between the inclusions.

Shared idiotypy among patients with myeloperoxidase-anti-neutrophil cytoplasmic autoantibody associated glomerulonephritis and vasculitis.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been hypothesized to participate in the pathogenesis of necrotizing vasculitis based on their association with small vessel vasculitides and the in vitro ability of such antibodies to activate cytokine-primed neutrophils. Much remains to be elucidated about the factors responsible for the generation and perpetuation of these autoantibodies and the shaping of the ANCA immune response. This study evaluated the clonal diversity of the ANCA immune response in patients with myeloperoxidase-ANCA associated disease. Isoelectric focusing was used to investigate the clonality of myeloperoxidase-ANCA from 34 patients with pauci-immune necrotizing glomerulonephritis. Sixty-nine percent of the patients had two or less clonotypes to myeloperoxidase, whereas 31% had more than two clonotypes. Clonality was stable over the course of the disease and shared among some unrelated patients. Shared idiotypy was specifically investigated using a murine monoclonal anti-idiotype (7F2C11) to the anti-myeloperoxidase antibodies of one patient with ANCA associated vasculitis. This monoclonal antibody was selected by demonstrating: (1) binding to the proband's affinity purified anti-myeloperoxidase antibodies; (2) an inhibitory effect on the binding of the proband's anti-myeloperoxidase to myeloperoxidase; and (3) lack of binding to control human antibody preparations, or to the proband's crude immunoglobulin preparation, thus excluding an anti-allotype antibody. Purified 7F2C11 was immobilized on Sepharose, and this monoclonal anti-idiotype affinity column was used to search for a shared anti-myeloperoxidase idiotype in the plasma of four other patients with myeloperoxidase-ANCA associated disease. Using this column, we were able to extract anti-myeloperoxidase antibodies from plasma of the other patients but not from control antibody preparations. We concluded that most myeloperoxidase-ANCA patients have a restricted response to myeloperoxidase and that some patients share a common idiotype. The demonstration of shared idiotypy suggests a restricted number of autoreactive epitopes of the myeloperoxidase molecule, or that some anti-myeloperoxidase autoantibodies are encoded by germ line genes, or both.

Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis.

The purpose of this study was to determine the prognostic value of clinical, laboratory, and pathologic features at the time of presentation on patient and renal survival in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated microscopic polyangiitis and glomerulonephritis (excluding Wegener's granulomatosis). One hundred seven ANCA-positive patients with necrotizing and crescentic glomerulonephritis, including 69 with evidence for microscopic polyangiitis, were evaluated for this study. The relative risk of death was calculated for the following potential prognostic indicators: (1) ANCA pattern; (2) pulmonary hemorrhage at onset; (3) presence of extrarenal manifestations versus renal limited disease; and (4) treatment with corticosteroids and cyclophosphamide (intravenous or oral), compared with corticosteroids alone. Cox's proportional hazard model was used to assess the predictive value of the following variables on renal survival: (1) age; (2) race; (3) pulmonary symptoms at onset of disease; (4) renal pathology; (5) ANCA pattern; and (6) peak serum creatinine values obtained near the time of renal biopsy. Patients were followed prospectively for 2.5 yr (range, 5 days to 12 yr 2 months). There were 12 disease-related deaths and 46 patients who reached ESRD. The relative risk (and 95% confidence interval) of patient death was 8.65 (3.36, 22.2) times greater in patients who presented with pulmonary hemorrhage, and 3.78 (1.22, 11.70) times greater in patients with cytoplasmic ANCA compared to those with perinuclear ANCA. The relative risk of pulmonary hemorrhage was no different by ANCA pattern. The risk of death was 5.56 times lower in the cyclophosphamide-treated patients versus those treated with corticosteroids alone. The predictors of renal survival were entry serum creatinine value (P = 0.0002), race (African Americans having a worse outcome compared with Caucasians, P = 0.0008), and the presence of arterial sclerosis on kidney biopsy (P = 0.0076) when controlling for age, ANCA pattern, microscopic polyangiitis versus glomerulonephritis alone, and pulmonary involvement. Pathology indices such as glomerular necrosis, glomerular crescents, glomerular sclerosis, and interstitial sclerosis were not predictive of renal survival when controlling for entry serum creatinine value, race, and arterial sclerosis. However, in the subgroup of patients with a peak creatinine value of < or = 3.0 mg/dL (N = 29), increased interstitial sclerosis was a predictor of a poor renal outcome (P = 0.04).

Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis.

In this study, the rate of remission, relapse, and treatment resistance in 107 patients with microscopic polyangiitis and necrotizing and crescentic glomerulonephritis associated with antineutrophil cytoplasmic autoantibodies were assessed. Patients with Wegener's granulomatosis were excluded. Prospective criteria were identified to assess remission, relapse, and resistant disease. Ninety-seven of the 107 patients received treatment with corticosteroids (N = 25) or with cyclophosphamide and corticosteroids (N = 72). Of these patients, 75 (77.3%) went into remission (complete remission, N = 61; remission on therapy, N = 14). Of the 75 responders, 32 patients (43%) remained in long-term remission, for a mean follow-up of 44 +/- 29 months; 15 patients (20%) progressed to ESRD without signs of relapse, for a mean of 21.4 +/- 22.8 months after the end of treatment; 6 patients died. Twenty-two of the 75 patients who initially responded to treatment (29%) suffered a relapse that occurred within 18 months of the end of therapy and usually affected the same organ systems as on initial presentation. There was a significant difference in the remission rate between the corticosteroid-treated patients and the cyclophosphamide-treated patients (56% versus 84.7%, P = 0.003), and the cyclophosphamide-treated patients had three times less risk of experiencing a relapse than did corticosteroid-treated patients (0.31, 95% Cl = (0.12, 0.84)). Seventy-seven percent (17 of 22 patients) of treatment resistance occurred in patients who presented with fulminant disease or advanced and severe renal disease. It was concluded that most patients with microscopic polyangiitis or necrotizing and crescentic glomerulonephritis achieve remission with therapy. Relapses occur in 29% of patients and generally respond to retreatment. Initial treatment with cyclophosphamide and corticosteroids rather than corticosteroids alone results in a lower frequency of relapse. Even patients who require dialysis at presentation may benefit from treatment, however, patients who are not treated until the disease process is life-threatening may die before induction therapy is complete, indicating the continued need for early diagnosis and therapy.

Conditional-firing aerosol-fluorescence spectrum analyzer for individual airborne particles with pulsed 266-nm laser excitation.

We report the operation of an aerosol-fluorescence spectrum analyzer capable of selectively measuring the fluorescence spectra of single micrometer-sized aerosol particles as they flow through the instrument. As the particle first traverses a cw 488-nm probe laser beam, the total fluorescence and elastic scattering are measured with photomultipliers. When the photomultiplier output levels meet preset logic conditions, a UV laser (at 266 nm) is fired and the particle fluorescence spectrum is recorded. Fluorescence spectra of biological airborne particles are presented. The ability of the analyzer to capture the fluorescence spectrum of one type of particle while ignoring others, based on the particle characteristics, is also demonstrated.

Conditional-sampling spectrograph detection system for fluorescence measurements of individual airborne biological particles.

We report the design and operation of a prototype conditional-sampling spectrograph detection system that can record the fluorescence spectra of individual, micrometer-sized aerosols as they traverse an intense 488-nm intracavity laser beam. The instrument's image-intensified CCD detector is gated by elastic scattering or by undispersed fluorescence from particles that enter the spectrograph's field of view. It records spectra only from particles with preselected scattering-fluorescence levels (a fiber-optic-photomultiplier subsystem provides the gating signal). This conditional-sampling procedure reduces data-handling rates and increases the signal-to-noise ratio by restricting the system's exposures to brief periods when aerosols traverse the beam. We demonstrate these advantages by reliably capturing spectra from individual fluorescent microspheres dispersed in an airstream. The conditional-sampling procedure also permits some discrimination among different types of particles, so that spectra may be recorded from the few interesting particles present in a cloud of background aerosol. We demonstrate such discrimination by measuring spectra from selected fluorescent microspheres in a mixture of two types of microspheres, and from bacterial spores in a mixture of spores and nonfluorescent kaolin particles.

Nonlinear outcoupling mechanism in a cylindrical dielectric microcavity supporting stimulated Raman scattering.

We describe a previously unreported nonlinear scattering effect that occurs in cylindrical liquid jets irradiated by an intense laser pulse. The spatial characteristics of this feature are quite striking: light emanating from a thin (

Aerosol-fluorescence spectrum analyzer: real-time measurement of emission spectra of airborne biological particles.

We have assembled an aerosol-fluorescence spectrum analyzer (AFS), which can measure the fluorescence spectra and elastic scattering of airborne particles as they flow through a laser beam. The aerosols traverse a scattering cell where they are illuminated with intense (50 kW/cm(2)) light inside the cavity of an argon-ion laser operating at 488 nm. This AFS can obtain fluorescence spectra of individual dye-doped polystyrene microspheres as small as 0.5 µm in diameter. The spectra obtained from microspheres doped with pink and green-yellow dyes are clearly different. We have also detected the fluorescence spectra of airborne particles (although not single particles) made from various biological materials, e.g., Bacillus subtilis spores, B. anthrasis spores, riboflavin, and tree leaves. The AFS may be useful in detecting and characterizing airborne bacteria and other airborne particles of biological origin.

Coherent stimulated Raman emission from a microcavity-excited optical resonator.

We report the observation of coherent emission from a planar Fabry-Perot resonator driven by a single, coherently emitting microcavity. The microcavity, either a liquid microdroplet or microcylinder, emits coherent stimulated Raman scattering when irradiated by an intense pump laser; the Raman light, in turn, couples to modes of the resonator. The spatiotemporal characteristics of resonator emission are strongly influenced by the microcavity source within; notably, a significant excess time delay in the emission of stimulated Raman scattering (i.e., compared with that of the microcavity in free space) accompanies the appearance of a sharp resonator spatial interference pattern. This and other noteworthy features are described, and a qualitative discussion of their significance is given.