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Cell-mediated immune response in the mammary gland of guinea pigs adoptively sensitized with lymphocytes.

Guinea pigs were vaccinated intramammarly (IMM) with attenuated Mycobacterium bovis (BCG) and challenged intramammarly and intradermally with tuberculin. A significant (p less than 0.05) milk leukocytosis, consisting primarily of polymorphonuclear leukocytes, occurred from 6-30 hr after challenge with tuberculin. Intradermal challenge with tuberculin produced typical delayed-type hypersensitivity cutaneous reaction in these animals. Normal guinea pigs were adoptively sensitized with lymphoid cells from the inguinal lymph nodes or spleen of BCG-vaccinated animals and subsequently challenged intramammarly and intradermally with tuberculin. The mammary and dermal responses of the lymphoid cell recipients were similar to, but less pronounced, than those in the actively immunized animals. The responses in the recipients of lymphocytes from donors injected with tuberculin 18 hr prior to cell collection were greater than those from injected donors. Guinea pigs that were injected intraperitoneally with serum from BCG-vaccinated donors did not express significant dermal or mammary responses to subsequent challenge with tuberculin. It was proposed that the milk leukocytosis was mediated by sensitized lymphocytes stimulated by IMM challenge with tuberculin.

Animals↗

Radiation-induced inflammatory malignant fibrous histiocytoma of the ileum.

A case of inflammatory malignant fibrous histiocytoma of the ileum seemingly induced by radiation is described. A 50-year-old female with a past history of uterine cervical carcinoma and postoperative radiation therapy presented with abdominal pain, fever and leukocytosis. The subserosa of the distal part of the ileum showed a diffuse dense, neutrophilic and lymphocytic infiltrate with dispersed atypical, short spindle- or plump oval-shaped histiocyte-like cells. Pleomorphic mono- or multinucleated giant cells with bizarre nuclei were also intermingled in the lesion. Immunohistochemically, the tumorous atypical cells were positive for vimentin, alpha-smooth muscle actin, alpha-1 antitrypsin and granulocyte colony-stimulating factor. No EBV genomic sequences were detected by in situ hybridization. Flow cytometry showed an aneuploid DNA content with high S-phase fraction. The patient was well with no evidence of tumor at 5 months after surgery. It is important to include this type of tumor in the differential diagnosis of small intestinal lesions accompanied by fever and leukocytosis following radiation.

Female↗

Role of leukocyte-endothelium adhesion in affecting recovery from ischemic episodes.

The role of the inflammatory process in the onset of sickle cell crisis has not been fully elucidated, although there is evidence for leukocytosis and enhanced leukocyte to endothelium adhesion. The elevated LEA typical of inflammation may impede recovery from transient ischemic episodes by increasing the resistance to blood flow, which in the case of sickle cell disease may exacerbate the "vicious cycle" of HbS deoxygenation which leads to microvascular stasis. Recent studies on the mechanics of white blood cell margination and adhesion in postcapillary venules of laboratory animals, either in the low-flow state or following tissue exposure to chemoattractants, reveal a marked rise in intravascular resistance with LEA. Such increases may be as great as twofold with as few as 6 WBCs adhering per 100 microns of venule length. In human subjects, leukocytosis attendant to crisis has been correlated with increased time to recover from induced periods of ischemia in skin capillaries. Thus, further definition of the role of the inflammatory process in crisis is needed in light of microvessel obstruction in the low-flow state.

Anemia, Sickle Cell↗

Haematological and biochemical investigations of diseased koalas (Phascolarctos cinereus).

Haematological and biochemical investigations were performed on 14 koalas with uncomplicated cystitis, 8 with complicated cystitis, 8 with conjunctivitis, 8 with lymphosarcoma, and 14 with miscellaneous diseases. Changes were limited and inconsistent in individual koalas with uncomplicated cystitis and conjunctivitis. In contrast, individual koalas with complicated cystitis were more likely to have anaemia, leukocytosis due to neutrophilia, hypoproteinaemia due to hypoalbuminaemia, and azotaemia due to elevated urea concentration. Although these changes were non-specific they did allow assessment of prognosis for survival and response to treatment. Koalas with lymphosarcoma were invariably anaemic, leukaemic, azotaemic and hypoalbuminaemic. Elevated enzymes (aspartate transaminase [AST]. lactate dehydrogenase [LD] and gamma glutamyl transferase [GGT]) were more common in koalas with lymphosarcoma. Koalas affected by miscellaneous conditions showed variable changes but once again anaemia, leukocytosis, azotaemia, elevated AST and LD, and hypoalbuminaemia were not uncommon. On the basis of these findings a minimal profile is suggested for the investigation of sick koalas and would include haematocrit, total and differential leukocyte counts, urea, total protein and albumin concentrations and AST, GGT and LD activities.

Animals↗

Comparison of white blood cell differential percentages determined by the in-house LaserCyte hematology analyzer and a manual method.

BACKGROUND: The LaserCyte hematology analyzer (IDEXX Laboratories, Chalfont St. Peter, Bucks, UK) is the first in-house laser-based single channel flow cytometer designed specifically for veterinary practice. The instrument provides a full hematologic analysis including a 5-part WBC differential (LC-diff%). We are unaware of published studies comparing LC-diff% results to those determined by other methods used in practice. OBJECTIVE: To compare LC-diff% results to those obtained by a manual differential cell count (M-diff%). METHODS: Eighty-six venous blood samples from 44 dogs and 42 cats were collected into EDTA tubes at the Forest Veterinary Centre (Epping, UK). Samples were analyzed using the LaserCyte within 1 hour of collection. Unstained blood smears were then posted to Langford Veterinary Diagnostics, University of Bristol, and stained with modified Wright's stain. One hundred-cell manual differential counts were performed by 2 technicians and the mean percentage was calculated for each cell type. Data (LC-diff% vs M-diff%) were analyzed using Wilcoxon signed rank tests, Deming regression, and Bland-Altman difference plots. RESULTS: Significant differences between methods were found for neutrophil and monocyte percentages in samples from dogs and cats and for eosinophil percentage in samples from cats. Correlations (r) (canine/feline) were .55/.72 for neutrophils, .76/.69 for lymphocytes, .05/.29 for monocytes and .60/.82 for eosinophils. Agreement between LC-diff% and Mdiff% results was poor in samples from both species. Bland-Altman plots revealed outliers in samples with atypical WBCs (1 cat), leukocytosis (2 dogs, 9 cats), and leukopenia (16 dogs, 11 cats). The LaserCyte generated error flags in 28 of 86 (32.6%) samples, included 7 with leukopenia, 8 with lymphopenia, 7 with leukocytosis, 1 with anemia, and 1 with erythrocytosis. When results from these 28 samples were excluded, correlations from the remaining nonflagged results (canine/feline) were .63/.65 for neutrophils, .67/.65 for lymphocytes, .11/.33 for monocytes, and .63/.82 for eosinophils. CONCLUSION: Although use of a 100-cell (vs 200-cell) M-diff% may be a limitation of our study, good correlation between WBC differentials obtained using the LaserCyte and the manual method was achieved only for feline eosinophils.

Animals↗

Use of IMiD3, a thalidomide analog, as an adjunct to therapy for experimental tuberculous meningitis.

Tuberculous meningitis (TBM), the most severe form of Mycobacterium tuberculosis infection in humans, is associated with significant morbidity and mortality despite successful treatment with antituberculous drugs. This is due to the irreversible brain damage subsequent to the local inflammatory response of the host to M. tuberculosis. Corticosteroids have been used in conjunction with antituberculous therapy in an attempt to modulate the inflammatory response, but this strategy has been of limited success. Therefore, we examined whether combining antituberculous drugs with the immunomodulatory drug thalidomide or with a new thalidomide analog, immunomodulatory drug 3 (IMiD3), would be effective in reducing morbidity and mortality in an experimental rabbit model of TBM. Intracisternal inoculation of 5 x 10(4) CFU of Mycobacterium bovis Ravenel in rabbits induced progressive subacute meningitis characterized by high cerebrospinal fluid (CSF) leukocytosis, protein influx, release of tumor necrosis factor (TNF), substantial meningeal inflammation, and mortality by day 28. Treatment with antituberculous drugs or with antituberculous drugs plus thalidomide improved the clinical course of disease somewhat and increased survival to about 50%. In contrast, treatment with antituberculous drugs in combination with IMiD3 limited pathological neurologic changes and resulted in marked improvement (73%) in survival. IMiD3 treatment was also associated with reduced leukocytosis in the CSF and significantly lower levels of TNF in CSF and plasma. Histologically, the meningeal inflammation in animals treated with antituberculous drugs plus IMiD3 was considerably attenuated compared to that of the other treatment groups. These results suggest a potential role for IMiD3 in the management of TBM in patients.

Animals↗

Pertussis toxin analog with reduced enzymatic and biological activities is a protective immunogen.

Bordetella pertussis TOX3201 has a 12-base-pair insertion in the S1 subunit gene of pertussis toxin (PTX), which encodes for a 4-amino-acid insertion between residues 107 and 108 of the mature S1 subunit (Black et al., Science 240:656-659, 1988). This mutant strain has been shown to secrete a holotoxin analog of PTX, designated CRM3201, with reduced ADP-ribosyltransferase activity. In the present study, we evaluated the biochemical, biological, and immunoprotective activities of purified CRM3201. Assay of enzymatic activities showed that CRM3201 had 20 to 30% of the ADP-ribosyltransferase activity and 55 to 60% of the NAD glycohydrolase activity of native PTX. CRM3201, however, had only 2 to 6% of the activity of PTX in clustering CHO cells, promoting leukocytosis, inducing histamine sensitization, and potentiating an anaphylactic response to bovine serum albumin. In contrast, activities associated with the B oligomer (binding to fetuin, hemagglutination of goose erythrocytes, and lymphocyte mitogen activity) were comparable to those of native PTX. Injection of BALB/c mice with CRM3201 mixed with Al(OH)3 elicited high titers of antibody to PTX (as measured by enzyme-linked immunosorbent assay), which neutralized a leukocytosis-promoting dose of PTX in these mice and neutralized PTX in a CHO cell assay. Passive transfer of the anti-CRM3201 antibody protected 20-day-old Swiss-Webster mice against a lethal aerosol challenge with B. pertussis 18323. Active immunization with CRM3201 significantly reduced lung colonization in adult BALB/c mice with a B. pertussis respiratory infection. These results demonstrate (i) that the reduced ADP-ribosyltransferase activity of CRM3201 is associated with reductions in certain biological and toxic activities of PTX (the enzymatic and biological activities are not, however, totally concordant); (ii) that CRM3201 possesses a functional B oligomer; and (iii) that CRM3201 can induce toxin-neutralizing antibodies which protect mice against a respiratory challenge with B. pertussis. Our studies with CRM3201 show that recombinant analogs of PTX have the potential to be developed into safe, protective immunogens for use in new acellular pertussis vaccines.

Anaphylaxis↗

MDHM, a macrophage-stimulatory product of Mycoplasma fermentans, leads to in vitro interleukin-1 (IL-1), IL-6, tumor necrosis factor, and prostaglandin production and is pyrogenic in rabbits.

Mycoplasma fermentans-derived high-molecular-weight material (MDHM) was originally discovered because of its capacity to generate, through the induction of monokine synthesis, cytolytic T lymphocytes in concanavalin A-stimulated thymocyte cultures. This study shows that MDHM-activated macrophages not only released interleukin-6 (IL-6) but also exhibited increased synthesis of cell-associated IL-1 as well as liberation of tumor necrosis factor and prostaglandin. We determined 6-keto prostaglandin F1 alpha since it is the stable metabolite of the bioactive prostacyclin. MDHM appeared to be as potent as lipopolysaccharide in inducing the synthesis of these mediators. Priming with gamma interferon further increased MDHM-mediated IL-6 release. Since monokines can be pyrogenic, we tested the effects of an intravenous injection of MDHM on rectal temperatures and leukocyte counts in rabbits. At 1 h after a bolus injection of MDHM, leukocyte counts dropped to about 35% of the initial values, reflecting a decrease in both lymphocytes and granulocytes. At 4 to 6 h after injection, granulocyte counts began to increase again, whereas lymphocyte counts remained low. No leukocytosis was noted during this time. The lack of leukocytosis can be explained by the failure of MDHM-stimulated macrophages to release IL-1. The property of MDHM to cause IL-6 release from macrophages and the IL-6 growth dependency of the 7TD1 hybridoma cell line were made use of in a coculture assay system to quantitate the activity of MDHM. With this method and macrophages from C3H/HeJ lipopolysaccharide-nonresponder mice, MDHM activity was found to be equally distributed in the mycoplasma growth medium and the sedimented mycoplasmas after sonication.

Animals↗

Quantitative priming with inactivated pertussis toxoid vaccine in the aerosol challenge model.

Serum antibodies to pertussis toxin (PT) have been shown to be protective against severe pertussis disease, although a specific level of anti-PT antibody that correlates with protection has not been demonstrated. Current animal models such as the intracerebral challenge model have significant limitations in correlating protection to a specific level of anti-PT antibody. This study examines the protective effects of priming with tetranitromethane-inactivated pertussis toxoid (PTx) vaccine in the aerosol challenge model and whether a measurable response to a priming dose of PTx is enough to initiate a protective secondary response when challenged with infection. The correlation of priming with markers of illness such as leukocytosis, weight loss, bacterial proliferation, and mortality after established infection with Bordetella pertussis was explored. BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. Data were analyzed according to the primary immunologic response, differentiating responders (anti-PT immunoglobulin G [IgG] > or =1 microg/ml) from nonresponders (anti-PT IgG <1 microg/ml). Mice that showed evidence of priming on the day of aerosol challenge were able to mount a secondary response to the challenge with a > or =2-fold rise in anti-PT IgG antibody by day 7 and a > or =10-fold rise by day 14 post-aerosol challenge. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge.

Aerosols↗

Host resistance of CD18 knockout mice against systemic infection with Listeria monocytogenes.

Mice with targeted mutations of CD18, the common beta2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a gram-positive extracellular bacterium. Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a gram-positive intracellular bacterium. We induced systemic listeriosis in CD18 knockout (CD18-ko) and wild-type (WT) mice by tail vein injection with Listeria. By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (P < 0.01). Quantitative organ culture showed that numbers of Listeria organisms in livers and spleens were similar in both groups at 20 min postinfection. By 3, 5, and 7 dpi, however, numbers of Listeria organisms were significantly lower in livers and spleens of CD18-ko mice than in WT mice. Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice. Cytokine assays indicated that baseline interleukin-1beta and granulocyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT mice and that CD18-ko splenocytes produced higher levels of interleukin-1beta and G-CSF than WT splenocytes under the same amount of Listeria stimulation. These findings show that CD18 is not an absolute requirement for antilisterial innate immunity or hepatic neutrophil recruitment. We propose that the absence of CD18 in the mice results in the priming of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments antilisterial defense.

Animals↗

Evaluation of the Mtb72F polyprotein vaccine in a rabbit model of tuberculous meningitis.

Using a rabbit model of tuberculous meningitis, we evaluated the protective efficacy of vaccination with the recombinant polyprotein Mtb72F, which is formulated in two alternative adjuvants, AS02A and AS01B, and compared this to vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) alone or as a BCG prime/Mtb72F-boost regimen. Vaccination with Mtb72F formulated in AS02A (Mtb72F+AS02A) or Mtb72F formulated in AS01B (Mtb72F+AS01B) was protective against central nervous system (CNS) challenge with Mycobacterium tuberculosis H37Rv to an extent comparable to that of vaccination with BCG. Similar accelerated clearances of bacilli from the cerebrospinal fluid, reduced leukocytosis, and less pathology of the brain and lungs were noted. Weight loss of infected rabbits was less extensive for Mtb72F+AS02A-vaccinated rabbits. In addition, protection against M. tuberculosis H37Rv CNS infection afforded by BCG/Mtb72F in a prime-boost strategy was similar to that by BCG alone. Interestingly, Mtb72F+AS01B induced better protection against leukocytosis and weight loss, suggesting that the polyprotein in this adjuvant may boost immunity without exacerbating inflammation in previously BCG-vaccinated individuals.

Adjuvants, Immunologic↗

Lymphocytosis and histamine sensitization of mice by fractions from Bordetella pertussis.

Administration of Bordetella pertussis cell extracts induced in mice hypersensitivity to histamine, as well as pronounced leukocytosis and hypoglycemia. The leukocytosis was mainly caused by an increase in the small lymphocytes in the circulating blood, and it was most pronounced 3 to 4 days after injection of B. pertussis extracts. Rabbit antimouse lymphocyte serum produced a decrease in the lymphocyte count in normal mice, as well as in mice treated with B. pertussis extracts. This depression in lymphocytes was observed whether the antilymphocyte serum was given 1 day or 2 days after the administration of B. pertussis extracts. The increased histamine sensitivity and hypoglycemia of mice treated with B. pertussis extract were not affected by treatment with antilymphocyte serum, although a marked lymphopenia was present. These observations indicate that the three phenomena observed in pertussis-treated mice are independent of each other.

Animals↗

Bacterial meningitis associated with lumbar drains: a retrospective cohort study.

OBJECTIVES: The infective potential of lumbar drainage is an important topic deserving particular study. The aetiology, incidence, and clinical findings associated with bacterial meningitis are described in patients having continuous lumbar CSF drainage to treat communicating hydrocephalus after subarachnoid haemorrhage or CSF leaks after traumatic dural rents. METHODS: Retrospective review of the records of patients with a positive CSF bacterial culture who underwent lumbar drain placement over a 39 month period. RESULTS: Thirteen cases of bacterial meningitis occurred subsequent to the use of 312 lumbar drain kits (4.2%). All meningitic patients had CSF pleocytosis, but not all had peripheral leukocytosis. Fever, peripheral leukocytosis, and CSF pleocytosis did not help to differentiate the presence of bacterial meningitis from other infections. Eight patients had prior CSF drainage procedures, including ventriculostomy (n=5) or lumbar drain (n=5) placements; two patients received both procedures. Six of 13 patients developed their CSF infection within 24 hours of lumbar drain insertion. Six of 13 patients developed meningitis while receiving antibiotics for other reasons. CONCLUSIONS: External lumbar drainage seems to carry a low risk of infectious meningitis and offers a safe alternative to ventriculostomy or serial lumbar punctures. Antibiotics do not seem to protect completely against developing the infection. The infection happens most often with skin organisms. The meningitis often appears within 24 hours after lumbar drain placement. Daily CSF samples should include bacterial cultures but cell counts may not offer any additional useful information in diagnosing the complication. Lumbar drain insertion and management need not be confined to the intensive care unit.

Adult↗

Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow.

Recombinant human interleukin-6 (IL-6) causes both a thrombocytosis and leukocytosis. The thrombocytosis is caused by an accelerating thrombocytopoiesis, but the mechanism of the leukocytosis is unknown. This study was designed to determine the relative contributions of marrow stimulation and intravascular demargination to the IL-6 induced neutrophilia. IL-6 (2 microgram/kg), administered intravenously to rabbits, caused a biphasic neutrophilia with an initial peak at 3 h and a second peak at 9 h. Using the thymidine analog 5'-bromo-2'-deoxyuridine (BrdU) to label dividing polymorphonuclear leukocytes (PMNs) in the bone marrow, we showed that IL-6 treatment mobilizes PMNs from the marginated pool into the circulating pool at 2-6 h with a decrease in L-selectin expression on PMNs and also accelerates the release of PMNs from the postmitotic pool in the bone marrow at 12-24 h. We have concluded that IL-6 causes a biphasic neutrophilia wherein the first peak results from the mobilization of PMNs into the circulating pool from the marginated pool and the second peak results from an accelerated bone marrow release of PMNs.

Animals↗

Contribution of exertional hyperthermia to sympathoadrenal-mediated lymphocyte subset redistribution.

The contribution of hyperthermia to the differential leukocytosis of exercise remains obscure. This study examined changes in circulating sympathoadrenal hormone concentrations and patterns of leukocyte and lymphocyte subset (CD3(+), CD4(+), CD8(+), CD19(+), CD3(-)16(+)/56(+)) redistribution during exercise, with and without a significant rise of rectal temperature (T(re)). Ten healthy men [age 26.9 +/- 5.7 (SD) yr, body mass 76.0 +/- 10.9 kg, body fat 13.9 +/- 4.6%, peak O(2) consumption: 48.0 +/- 12.4 ml x kg(-1) x min(-1)] exercised for 40 min (65% peak O(2) consumption) during water immersion at 39 or 18 degrees C. T(re) increased from 37.2 to 39.3 degrees C (P < 0.0001) after 40 min of exercise in 39 degrees C water but was held constant to an increment of 0.5 degrees C during exercise in 18 degrees C water. Application of this thermal clamp reduced exercise-associated increments of plasma epinephrine (Epi) and norepinephrine (NE) by >50% (P < 0.05) and abolished the postexercise increase in cortisol. Thermal clamping also reduced the exercise-induced leukocytosis and lymphocytosis. Multiple regression demonstrated that T(re) had no direct association with lymphocyte subset mobilization but was significantly (P < 0.0001) correlated with hormone levels. Epi was an important determinant of total leukocytes, lymphocytes, and CD3(+), CD4(+), CD8(+), and CD3(-)CD16(+)/56(+) subset redistribution. The relationship between NE and lymphocyte subsets was weaker than that with Epi, with the exception of CD3(-)CD16(+)/56(+) counts, which were positively (P < 0.0001) related to NE. Cortisol was negatively associated with leukocytes, CD14(+) monocytes, and CD19(+) B- and CD4(+) T-cell subsets but was positively related to granulocytes. We conclude that hyperthermia mediates exercise-induced immune cell redistribution to the extent that it causes sympathoadrenal activation, with alterations in circulating Epi, NE, and cortisol.

Adrenal Glands↗

Stroke in hospitalized patients: are there special risk factors?

BACKGROUND AND PURPOSE: The occurrence of stroke in patients hospitalized for various illnesses remains a particular challenge for neurologists. Determining the potential causes for these particular cerebrovascular events may help to define the population at risk and to take measures in order to prevent stroke during hospitalization. The aim of our study was to evaluate the potential risk factors associated with stroke, which occurred in patients hospitalized for other illnesses. METHODS: This retrospective case-control study based on data of patients who underwent an ischemic stroke while being hospitalized not because of stroke and a control group of patients admitted during the same period who were matched for age and sex to the study patients. Common vascular risk factors, e.g. fever, leukocytosis, blood pressure, hemoglobin, cardiac arrhythmia and dehydration, were compared between the study and control groups. RESULTS: Of 2,247 consecutive patients with ischemic stroke, the stroke had occurred during hospitalization not related to any surgical procedure in 80 (3.5%). Six parameters were found as being significant independent risk factors for in-hospital stroke: fever and leukocytosis during hospitalization, elevated diastolic and unstable blood pressure, dehydration and past history of myocardial infarction. CONCLUSION: Careful monitoring of temperature, blood count, blood pressure, and clinical and laboratory signs of dehydration is needed to prevent in-hospital stroke.

Aged↗

Features of idiopathic pulmonary fibrosis with organizing pneumonia.

To characterize the clinical features of patients with idiopathic pulmonary fibrosis (IPF) having organizing pneumonia (OP), we retrospectively reviewed the clinical charts, chest X-rays, CT scans, and transbronchial lung biopsy (TBLB) specimens of patients with IPF. Patients with IPF and OP had a subacute onset of symptoms (within 2 months) (87.5%), leukocytosis (> 10,000/mm3) (62.5%), and a strong C-reactive protein (CRP) reaction (> 3+) (75%). Some of these features were distinctly different from those of IPF patients without OP (subacute onset of symptoms 0%, leukocytosis 0%, strong CRP reaction 16.7%). In the patients with IPF with OP, A-aDo2 and semiquantitative scores of chest X-ray abnormalities improved significantly after prednisolone treatment. Those abnormalities improved only slightly in the patients with IPF without OP. Diffusing capacity remained decreased and abnormal interstitial infiltration persisted, even after prednisolone treatment in the patients with IPF with or without OP. Clinical features of IPF patients with OP differed from those of patients with IPF without OP. IPF patients with OP showed good clinical response to corticosteroid therapy. These findings warrant further study of the presence of OP in TBLB specimens in predicting corticosteroid responsiveness and prognosis of patients with IPF.

Cryptogenic Organizing Pneumonia↗

Chronic neutrophilic leukemia associated with monoclonal gammopathy of undetermined significance.

A 30-year-old man with chronic neutrophilic leukemia (CNL) in association with monoclonal gammopathy is presented. Physical examination on admission revealed moderate hepatosplenomegaly. Initial blood count showed neutrophilic leukocytosis (42.2 x 10(9)/1 with 90% mature neutrophils). Leukocyte alkaline phosphatase (LAP) score was elevated. Bone marrow aspiration showed myeloid hyperplasia without dysplastic features. Karyotypic and molecular analyses of bone marrow cells showed the absence of Philadelphia (Ph1) chromosome and bcr gene rearrangement. Because there was no underlying infection or neoplasm, he was diagnosed as having CNL associated with IgG kappa-type monoclonal gammopathy (IgG, 1,269 mg/dl). In addition to its association with monoclonal gammopathy of undetermined significance (MGUS), the present case was also characterized by spontaneous remission of CNL during the 12-year follow-up, accompanied by a gradual increase in serum IgG levels up to 3,000 mg/dl. As far as we know, there have been 19 cases of CNL associated with monoclonal gammopathy in the literature. The median survival of these cases was 5 years. Although there have been only 6 cases of CNL associated with MGUS, survival of these cases was particularly favorable. Taken together with the observation that leukocytosis and hepatosplenomegaly in the present case subsided without specific treatment, we speculate that myeloid proliferation in the present case may have been a leukemoid reaction to underlying monoclonal gammopathy.

Adult↗