Absence Of Leukocytosis Research Articles

Human and entomological surveillance of West Nile fever, dengue and chikungunya in Veneto Region, Italy, 2010-2012

BackgroundSince 2010 Veneto region (North-Eastern Italy) planned a special integrated surveillance of summer fevers to promptly identify cases of West Nile Fever (WNF), dengue (DENV) and chikungunya (CHIKV). The objectives of this study were (i) To increase the detection rate of imported CHIKV and DENV cases in travellers from endemic areas and promptly identify potential autochthonous cases.(ii) To detect autochthonous cases of WNF, besides those of West Nile Neuroinvasive Disease (WNND) that were already included in a national surveillance.MethodsHuman surveillance: a traveler who had returned within the previous 15 days from endemic countries, with fever >38°C, absence of leucocytosis (leukocyte count <10,000 μL), and absence of other obvious causes of fever, after ruling out malaria, was considered a possible case of CHIKV or DENV. A possible autochthonous case of WNF was defined as a patient with fever >38°C for <7 days, no recent travel history and absence of other obvious causes of fever. Entomologic surveillance: for West Nile (WNV) it was carried out from May through November placing CDC-CO2 traps in five provinces of Veneto Region, while for DENV and CHIKV it was also performed around residences of viremic cases.ResultsHuman surveillance: between 2010 and 2012, 234 patients with fever after travelling were screened, of which 27 (11,5%) were found infected (24 with DENV and 3 with CHIKV). No autochthonous case of DENV or CHIKV was detected. Autochthonous patients screened for WNF were 408, and 24 (5,9%) were confirmed cases. Entomologic surveillance: the WNV was found in 10, 2 and 11 pools of Culex pipiens from 2010 to 2012 respectively, in sites of Rovigo, Verona, Venezia and Treviso provinces). No infected Aedes albopictus with DENV or CHIKV was found.ConclusionsVeneto is the only Italian region reporting WNV human cases every year since 2008. WNV is likely to cause sporadic cases and unforeseeable outbreaks for decades. Including WNF in surveillance provides additional information and possibly an early alert system. Timely detection of DENV and CHIKV should prompt vector control measures to prevent local outbreaks.

Appendicitis in the Absence of Leukocytosis; A Community Hospital Experience

Appendicitis in the Absence of Leukocytosis; A Community Hospital Experience

Correlation of polymorphisms in genes coding cytokines TNF-α, IL-10, MBL2, IFN-γ and IL-6 with complicated course of urogenital chlamydial infection in men

Goal. To develop a personified approach to the management of men with the urogenital chlamydia infection based on studying the molecular and genetic risk factors of the development of complications. Materials and methods. Patients with the urogenital chlamydia infection (20 men with the urogenital chlamydia infection of the lower urogenital tract and 20 men with complicated forms of the urogenital chlamydia infection) and men without any clinical or laboratory signs of STDs and inflammatory diseases of the urogenital tract. The following methods were used in the study: anamnestic, clinical, instrumental (transrectal ultrasonography) and laboratory (microscopic, bacteriological, molecular and biological (PCR, SNaPshot)). Results. According to the study results, the share of cases of ureteritis caused by C. trachomatis amounted to 10.5% of the total share of cases of ureteritis and 13.0% of cases of non-gonococcal ureteritis. The percentage of complicated urogenital diseases caused by C. trachomatis amounted to 34.5% of the total share of complicated forms and 35.7% of noncomplicated forms of the non-gonococcal origin. Subjective clinical signs of complicated forms of the chlamydia infection did not have any reliable distinctions from those observed in case of non-complicated forms of the disease; the infectious process caused by C. trachomatis was characterized by the absence of leukocytosis in the urethra in 30.0% of men with both non-complicated and complicated forms of the disease. The study of the polymorphism of cytokine genes revealed that the CC genotype of IL-6 gene at the -174 locus can serve as a molecular predictor of the complicated course of urogenital chlamydiosis in men while the GC genotype of IL-6 gene at the -174 locus can serve as a molecular predictor of the non-complicated course of urogenital chlamydiosis in men. Based on these results, the authors developed an algorithm for a differential approach to the management of patients suffering from chlamydia infection. Conclusion. A differential approach to the management of men with the urogenital chlamydia infection depending on the molecular predictor of the complicated course of the disease was developed.

Predictors of viral pneumonia: The need for viral testing in all patients hospitalized for nursing home‐acquired pneumonia

AimCommunity‐acquired pneumonia (CAP) is presumed to be bacterial in origin and empirical antibiotics are almost always given on admission. However, early detection of viral infection is also very important for hospital infection control and timely use of antiviral agents. The present study aimed to compare patients with viral and bacterial pneumonia, and identify independent predictors of viral pneumonia.MethodsA prospective cohort study was carried out in a tertiary teaching hospital in a 1‐year period. Older patients (aged ≥65 years) were recruited if they were admitted for CAP confirmed by chest radiographs.ResultsA cohort of 488 patients was analyzed. Infective causes were found in 137 (28.1%) patients. Bacterial, viral and mixed infections were detected in 86 (17.6%), 41 (8.4%) and 10 (2.0%) patients, respectively. Bacteriology was established mostly by sputum culture and virology by nasopharyngeal aspirate (NPA) viral culture. The commonest bacterial isolates were Haemophilus influenzae (31), Pseudomonas aeruginosa (15), Mycobacterium tuberculosis (14), Klebsiella spp. (9) and Streptococcus pneumoniae (6). Influenza A virus (28, 8 were pandemic 2009 A/H1N1 subtype) and respiratory syncytial virus (16) were the most frequent viral causes. Independent predictors of viral pneumonia included nursing home residence (RR 3.056, P = 0.009) and absence of leukocytosis (RR 0.425, P = 0.026).ConclusionsAll nursing home residents hospitalized for CAP should undergo NPA viral testing because of infection control, early antiviral treatment and discharge planning. We suggest that empirical antiviral agents might be considered for nursing home residents hospitalized for CAP if outbreaks of influenza‐like illness are reported in nursing homes. Geriatr Gerontol Int 2013; 13: 949–957.

Allergy to implants in lumbar screw fixation mimics postsurgical wound infection

Dear Editor, We report the case of a 44-year-old female patient with lumbo-ischialgic pain projecting to dermatomes S1. Conservative treatment was unsuccessful and the pain progressed until the patient was unable to walk. After lumbar computed tomography (CT) evaluation, a radicular compression due to listhesis could be seen in the level L5/S1 (Meyerding Grade I, Fig. 1a). Radicular decompression and screw fixation from L5 to S1 followed. The postoperative CT shows good screw position and dural decompression (Fig. 1b). At this point it is important to mention that the patient had allergies against sodium thiosulphate (dental products), 1,3-diphenylguanidine (rubber) and nickel (II) sulphate. No titanium allergy. Immediately post-surgery, the patient still complained of lumbo-ischialgic pain with a 7/10 visual analogue scale (VAS) score. Because of pain, ambulation was impossible (despite good postoperative results on CT). Inspection of the wound showed oedema, redness and hyperthermia resembling the clinical signs of wound infection. After microbiological screening (Staphylococcus epidermidis, Streptococcus oralis, Streptococcus faecalis and Staphylococcus haemoliticus positive), we started antibiotic treatment even in absence of leucocytosis or increased C-reactive protein. The pain persisted and a lumbar magnetic resonance imaging (MRI) 2 weeks post-surgery failed to show signs of post-operative infection. Irrespective of absence of inflammatory proteins in the serum and/or leucocytosis and under antibiotic treatment, there was putrid wound excretion. Surgical wound debridment followed. Intraoperativelly there was no dislocation of the screws. There were no signs of infection under the skin (i.e. epidural or lumbar bone). After wound-debridment there was still no improvement of pain (VAS 6/10). Creactive protein was normal. Because of persistence of symptoms, another lumbar CT followed 7 weeks postsurgery. No signs of screw dislocation were seen, but at this time there was subcutaneous air identifiable (subcutaneous infection?). MRI and serum failed to show infection. In a second wound debridment, granulation tissue was removed epidurally. The whole time the patient received antibiotic treatment. After two wound revisions we performed an epicutaneus allergy test. A titan screw like the ones used for fixation in the patient’s case was adhered for 48 h on the patient’s upper arm. After 48 h the patient exhibited an allergic reaction of the type IV (allergic contact dermatitis) (Fig. 2). Steel and PEEK cage did not resemble allergic reactions on the patient’s skin. In a third revision we changed the titanium screws with steel screws and a PEEK cage was placed in the intervertebral space L5/S1. Histopathologically, fat and muscle tissue from the wound showed lymphocytic inflammation and chronic inflammatory infiltrates. Immediately after the replacement of the titanium screws the patient showed an improvement of her symptoms (VAS 1/10), and could be discharged with minimal postoperative pain. In the MELISA (Memory Lymphocyte Immunostimulation Assay) test and the lymphocyte transformation test, no Rashad El Habony and Yucel Binay contributed equally

Clinical and morphological features of community-acquired pneumonia during the A / H1N1 influenza epidemics

Summary. This article presents a retrospective comparative analysis of hospitalized cases of community-acquired pneumonia (CAP) during the 2007 to 2009 years in a pneumology department of a regional hospital, Penza. This period included 2009 A / H1N1 influenza epidemics. In 2009, the number of hospitalizations increased in 1.4 times, mortality increased in 5.7 times in comparison with 2007 and 2008 years. Severe and atypical course of CAP with dry cough, prolonged fever, severe respiratory failure, bilateral multi-segmental lesions, an absence of leukocytosis and severe complications (acute respiratory failure, phlebitis, sepsis) were noted in 60.9 % of patients. CAP associated with influenza A / H1N1 was more common in patients with cardiovascular disease, obesity and differed from CAP in previous years. In 2009, outcomes of CAP were fibrosis in 43.8 % (compared to 25 % in 2008 and 21.2 % in 2007) and death in 12.5 % of cases. Pathomorphological findings were hemorrhage and microthrombosis in respiratory system, brain, and other organs.

True hypoglycaemia secondary to treatment with granulocyte colony stimulating factor (G-CSF) in a diabetic patient with non-small cell lung cancer

We report the case of a 61-year-old man with non-small lung cancer with poorly controlled type 2 diabetes mellitus who developed clinically significant hypoglycaemia secondary to a first exposure to granulocyte colony stimulating factor (G-CSF) injections. Whilst artefactual hypoglycaemia during treatment with G-CSF is well recognised, to our knowledge, this is the first report revealing that it can provoke true hypoglycaemia in the absence of leucocytosis.

Churg–Strauss syndrome with broad spectrum clinical presentations: a report of 3 cases

The American College of Rheuma• tology that has suggested 6 criteria from which 4 are required for a diagnosis of CSS with 99.7% specificity and 85% sensitivity. The 6 criteria include: asthma, eosinophilia > 10%, paranasal sinusitis, vasculitis based on histology, and mononeuritis multiplex [4]. Vasculitis lesions of CSS on histological examination are not typically seen in biopsies and are not specific for CSS; at the same time their absence is not cause to reject a diagnosis of CSS [5]. It is important to differentiate CSS from other systemic vasculitis because of the association between start of treatment and CSS prognosis [6,7]. In the present study, we report 3 CSS cases with diverse clinical presentations to investigate if a clinical approach and history of the patient could be diagnostic for CSS without invasive procedures such as histological confirmation by biopsy. We also sought to assess whether the absence of leukocytosis and eosinophilia could allow a diagnosis of CSS to be rejected.

Cytokine levels in bronchoalveolar lavage and serum in 3 patients with 2009 Influenza A(H1N1)v severe pneumonia

Pandemic Influenza A (H1N1)v pneumonia has led to a notable increase of admissions to intensive care units. A cytokine-mediated inflammatory response has been well documented in pneumonia and acute respiratory distress syndrome. However, few studies have focused on the role of these inflammatory mediators in infections caused by the Influenza A (H1N1)v. In this study, we assess the inflammatory response mediated by cytokines at the local and systemic levels in three cases of severe pneumonia caused by Influenza A (H1N1) virus. Serum and bronchoalveolar lavage samples were obtained from three mechanically ventilated patients diagnosed with Influenza A (H1N1) virus pneumonia by bronchoscopic bronchoalveolar lavage. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1ß) were meassured in these samples by enzyme-linked immunosorbent assay (ELISA). High levels of C Reactive Protein, Procalcitonin below 1 ng/ml and absence of leukocytosis were common findings in all patients. TNFα and IL-1ß were not detected in the serum. IL-6 levels in serum were (94, pg/ml, 77 pg/ml and 84 pg/ml) respectively in the three patients, while IL-8 levels were (30,2 pg/ml, 128 pg/ml and 40,5 pg/ml). In the BAL samples, only one of the analysed cytokines, IL-1ß was present at detectable levels in two patients (21 pg/ml and 11 pg/ml respectively). Our results support previous findings which suggest that high levels of IL-6 and IL-8 in serum somehow participate in the inflammatory response in severe cases of pandemic influenza pneumonia.

Absence of leukocytosis in bacteraemic pneumococcal pneumonia

Evaluation of patients with respiratory symptoms in primary care medicine is often based on peripheral WBC count that dictates the extent of diagnostic investigation. A normal WBC count may result in a limited investigation, often omitting chest radiography. To determine the extent to which patients hospitalised with bacteraemic pneumococcal pneumonia have no leukocytosis at presentation. A retrospective analysis was performed of patients with bacteraemic community-acquired pneumococcal pneumonia from 2000 to 2007 in a community care academic medical centre. Records were reviewed for symptoms, signs, and laboratory data including pneumococcal serotypes, chest radiographs on admission, and outcome. 21% of the patients presented with a normal WBC count (16.7% of the children and 25.6% of the adults). Among this population with a normal WBC count at presentation, 90% of the adults and 70% of the children developed leukocytosis within a few days after admission. In this study, in as many as one-fifth of all the patients with bacteraemic pneumococcal pneumonia, there was no leukocytosis at presentation. We therefore suggest that every patient with clinically suspected pneumonia should undergo chest radiography even if the WBC count is normal.

Association Between Use of Pain Medication, Ultrasound Findings, and Adnexal Torsion Among Young Females Presenting With Acute Abdominal Pain

day. To our knowledge, we report the first confirmed case of pediatric synchronous bilateral ovarian torsion in bilaterally normal ovaries and offer a review of the literature. Case: A previously healthy twelve year old female was seen in clinic with a two year history of recurrent right lower quadrant pain with no associated symptoms. Initial ultrasound showed normal ovaries. Repeat imaging ten months later revealed bilateral bulky ovaries: right ovary 43x32x38mm (20cc) and left ovary 56x35x55mm (52.3 cc). Peripheral follicles in keeping with polycystic ovaries were noted. The patient was not yet menarchal. Workup for celiac disease was negative. Shortly following this ultrasound, she presented to the emergency department with a thirty hour history of periumbilical pain associated with nausea and vomiting. On exam, the pain was localized to the left lower quadrant with rebound tenderness. There was absence of leukocytosis. Ultrasound showed a significantly enlarged left ovary (61x45x49mm; 70cc) with diminished flow on Doppler assessment. She underwent laparoscopy with a presumed diagnosis of left ovarian torsion. However, on entering the abdomen, bilateral ovarian torsion of 720o was detected (Figures 1 and 2). Both ovaries were enlarged, left greater than right, without obvious focal lesions. Uteroovarian ligaments were noted to be abnormally long. The ovaries were detorted and pexed to their respective uterosacral ligaments using an intracorporeal technique with nonabsorbable suture.

Apport de la scintigraphie osseuse dans le diagnostic des arthrites inflammatoires rares : à propos d’un cas de syndrome de Sapho à l’hôpital général de Grand Yoff

The SAPHO syndrome is suspected in a 47 years old Senegalese female patient with a swelling of medial quarter of the right clavicle, and a history of palmar pustulosis. The general state of health is preserved, biology shows a nonspecific inflammatory syndrome (elevated erythrocyte rate and C reactive protein level) and an absence of leukocytosis. Histopathological examination found a polymorphic inflammatory granuloma with mononuclear cells and giant cells. The standard radiographs and CT scans did not disclose any lesion while the bone scan displayed a “bull's horn” image of increased uptake on the right sterno-clavicular region suggestive of SAPHO syndrome. The frequent delay in diagnosis, usually related to ignorance of the syndrome and the fear of a bone tumour, is a major source of antibiotic abuse and/or biopsies, invasive or harmful for patients. Bone scintigraphy has a role to play in guiding the diagnosis when it discovers focal increased uptake on clavicle and sternum. May moreover, bone scintigraphy be useful to review and assess the distribution of lesions and their follow-up.

Adhesive small bowel obstruction in children: should we still operate?

Purpose Adhesive small bowel obstruction (ASBO) is a significant cause of postoperative morbidity, yet studies characterizing outcomes in children are limited. Our aim was to review our experience to describe the role of operative and nonoperative therapy, markers of outcome, and burden of disease in children. Materials and Methods Admissions for ASBO at British Columbia Children's Hospital (Vancouver, British Columbia, Canada) identified by International Classification of Disease, Ninth Revision, codes were reviewed over a 10-year period. Demographic, clinical, laboratory, and operative details were collected for all patients. Results Our study identified 165 admissions of which 32 (19%) were managed with immediate operation, whereas 133 were initially managed nonoperatively. One hundred seven patients went on to laparotomy, whereas 26 (16%) were managed nonoperatively. Absence of leukocytosis and older age appeared to be associated with successful nonoperative therapy. Tachycardia and younger age appeared to be independent risk factors for failure of nonoperative management. Delayed surgery or conservative management did not cause an increase in complications. Appendectomy, stoma formation and closure, Nissen fundoplication, and Ladd's procedures were the most common procedures leading to ASBO. Conclusions Conservative therapy is the preferred approach in selected patients with ASBO. However, 84% eventually require surgery. This differs markedly from results in adults where most resolve nonoperatively. Younger patients were more likely to fail conservative trials and were more likely to develop advanced disease, pointing to ASBO as a distinct disease entity in children.

Predictors of Mortality in Skin and Soft‐tissue Infections Caused by Vibrio vulnificus

Vibrio vulnificus infection can progress rapidly in skin or soft tissue, and it is potentially life-threatening. The purpose of the present study was to explore the predictors of mortality in patients with V. vulnificus infections of skin or soft tissue. The medical records of 119 consecutive patients aged > or =18 years, hospitalized for V. vulnificus infections of skin or soft tissue between January 2000 and December 2007 were reviewed. Co-morbidities, clinical manifestations, laboratory studies, treatments, and outcomes were analyzed. Multiple logistic regression with the exact method was performed. The mean age of the patients was 63.7 +/- 12.0 years. Twenty-four patients died, yielding an overall case fatality rate of 20%. Of the 24 deaths, 20 (83%) occurred within 72 h after hospital admission. Of 119 patients, 45 patients had primary septicemia, and 74 patients had wound infection. Multivariate analysis revealed that the following factors were associated with mortality: hemorrhagic bullous skin lesions/necrotizing fasciitis (p = 0.003), primary septicemia (p = 0.042), a greater organ dysfunction and/or infection score (p = 0.005), absence of leukocytosis (p = 0.0001), and hypoalbuminemia (p = 0.003). Treatment with surgical intervention plus antibiotics (p = 0.038) and surgical intervention within 24 h after admission (p = 0.017) were protective factors. This study demonstrates that the presence of hemorrhagic bullous skin lesions/necrotizing fasciitis, primary septicemia, a greater severity-of-illness, absence of leukocytosis, and hypoalbuminemia were the significant risk factors for mortality in these patients. Moreover, patients treated with surgery plus antibiotics, especially those receiving a prompt surgical evaluation within 24 h after hospital admission, may have a better prognosis.

Improving the Clinical Diagnosis of Influenza—a Comparative Analysis of New Influenza A (H1N1) Cases

BackgroundThe presentation of new influenza A(H1N1) is broad and evolving as it continues to affect different geographic locations and populations. To improve the accuracy of predicting influenza infection in an outpatient setting, we undertook a comparative analysis of H1N1(2009), seasonal influenza, and persons with acute respiratory illness (ARI) in an outpatient setting.Methodology/Principal FindingsComparative analyses of one hundred non-matched cases each of PCR confirmed H1N1(2009), seasonal influenza, and ARI cases. Multivariate analysis was performed to look for predictors of influenza infection. Receiver operating characteristic curves were constructed for various combinations of clinical and laboratory case definitions. The initial clinical and laboratory features of H1N1(2009) and seasonal influenza were similar. Among ARI cases, fever, cough, headache, rhinorrhea, the absence of leukocytosis, and a normal chest radiograph positively predict for both PCR-confirmed H1N1-2009 and seasonal influenza infection. The sensitivity and specificity of current WHO and CDC influenza-like illness (ILI) criteria were modest in predicting influenza infection. However, the combination of WHO ILI criteria with the absence of leukocytosis greatly improved the accuracy of diagnosing H1N1(2009) and seasonal influenza (positive LR of 7.8 (95%CI 3.5–17.5) and 9.2 (95%CI 4.1–20.3) respectively).Conclusions/SignificanceThe clinical presentation of H1N1(2009) infection is largely indistinguishable from that of seasonal influenza. Among patients with acute respiratory illness, features such as a temperature greater than 38°C, rhinorrhea, a normal chest radiograph, and the absence of leukocytosis or significant gastrointestinal symptoms were all positively associated with H1N1(2009) and seasonal influenza infection. An enhanced ILI criteria that combines both a symptom complex with the absence of leukocytosis on testing can improve the accuracy of predicting both seasonal and H1N1-2009 influenza infection.

Pomalidomide Is Active in the Treatment of Anemia Associated With Myelofibrosis

Thalidomide and lenalidomide can alleviate anemia in myelofibrosis. However, their value is undermined by their respective potential to cause peripheral neuropathy and myelosuppression. We therefore evaluated the safety and therapeutic activity of another immunomodulatory drug, pomalidomide. In a phase II randomized, multicenter, double-blind, adaptive design study, four treatment arms were evaluated: pomalidomide (2 mg/d) plus placebo, pomalidomide (2 mg/d) plus prednisone, pomalidomide (0.5 mg/d) plus prednisone, and prednisone plus placebo. Pomalidomide was administered for up to 12 28-day treatment cycles. Prednisone (30 mg/d) was given in a tapering dose schedule during the first three cycles. Response was assessed by International Working Group criteria. Eighty-four patients with myelofibrosis-associated anemia were randomly assigned to the aforementioned treatment arms: 22, 19, 22, and 21, respectively. Response in anemia was documented in 20 patients, including 15 who became transfusion independent. Response rates in the four treatment arms were 23% (95% CI, 5% to 41%), 16% (95% CI, 0% to 33%), 36% (95% CI, 16% to 56%), and 19% (95% CI, 2% to 36%). The corresponding figures for patients receiving > or = 3 cycles of treatment (n = 62) were 38%, 23%, 40%, and 25%. Response to pomalidomide with or without prednisone was durable (range, 3.2 to 16.9+ months) and significantly better in the absence of leukocytosis (37% v 8%; P = .01); JAK2V617F or cytogenetic status did not affect response. Grade > or = 3 toxicities were infrequent and included (in each treatment arm) neutropenia (9%; 16%; 5%; 5%), thrombocytopenia (14%; 16%; 9%; 5%), and thrombosis (9%; 5%; 0%; 0%). Pomalidomide therapy at 0.5 or 2 mg/d with or without an abbreviated course of prednisone is well tolerated in patients with myelofibrosis and active in the treatment of anemia.

Cytoreductive Therapy in Systemic Mastocytosis: Outcome Analysis and Response Prediction in 134 Consecutive Patients.

Background: Current therapy in adult systemic mastocytosis (SM) includes observation alone, topical therapy for cutaneous disease, symptomatic non-cytoreductive therapy and cytoreductive therapy. The latter involves several drugs whose individual merit in the treatment of SM has not been well characterized.Patients and Methods: Diagnosis of SM was according to the 2001 WHO criteria (World Health Organization Classification of Tumours of Hematopoietic and Lymphoid Tissues, p 1–351. Lyon, France: IARC Press; 2001). Response to cytoreductive therapy was assessed by consensus criteria (Eur J Clin Invest. 2007; 37:435). The study population was selected from a series of 342 adult SM patients referred to our institution and seen between 1964 and 2008. KITD816V mutation analysis was performed by DNA sequencing.Results: A total of 134 study patients received treatment that included at least one cytoreductive drug as either first-line (n=105) or second-line (n=29) therapy. Interferon-alpha with or without prednisone (n=58), hydroxyurea (n=43), imatinib mesylate (n=42) and 2-chlorodeoxyadenosine (n=26) were the most frequently used cytoreductive agents accounting for 120 of the 134 study cases; the remaining 14 patients received other cytoreductive drugs, none of which were effective. i. Interferon-alfa (IFN-a) with or without prednisone IFN-a with or without prednisone (24 and 34 patients, respectively) was given to 12 patients with indolent SM (ISM), 14 aggressive SM (ASM), and 32 SM with associated clonal hematological non-mast cell lineage disease (SM-AHNMD). For all 58 patients receiving therapy, complete (CR), major (MR), and partial (PR) response/regression were achieved in 3, 7, and 14 patients, respectively, for an overall response rate (ORR) of 41%. ORR in ISM, ASM, and SM-AHNMD was 50%, 43%, and 38%, respectively. Median duration of response was 12 months (range, 1–117 months). Anemia and elevated ESR were significantly associated with inferior ORR; 29% vs. 56% (p=0.04) and 14% vs. 57% (p=0.01), respectively. BM detection of KITD816V did not appear to affect response rates (p=0.4). ii. Hydroxyurea (HU) HU was given to 2 ASM, 40 SM-AHNMD and 1 mast cell leukemia (MCL) patients. The drug was used as first-line therapy in 30 patients. MR and PR were achieved in 1 and 8 SM-AHNMD patients, respectively (ORR=21%). Median duration of response was 37 months (range, 5–84 months). iii. Imatinib mesylate (IM) in patients with SM and associated eosinophilia IM was given to 22 SM patients who had associated eosinophilia (SM-eos): 2 had ISM, 2 ASM, and 18 SM-AHNMD. The drug was used as first-line therapy in 9 patients. Ten of the 22 patients with SM-eos were known to harbor the FIP1L1-PDGFRA fusion mutation and all responded to IM (ORR=100%). None of 5 FIP1L1-PDGFRA-negative SM-eos patients had a response to IM. In the remaining 7 patients with unknown mutation status, 4 patients had a response to IM (1 CR, 1 MR, and 2 PR). iv. IM in patients with SM not associated with eosinophilia IM was administered to 20 SM patients without associated eosinophilia (7 ISM, 2 ASM, 10 SM-AHNMD, and 1 MCL). Response was documented in 4 (20%) patients (1 CR, 1 MR, and 2 PR) including 1 with ISM, 2 with ASM and 1 with SM-AHNMD. Median duration of response was 19.5 months (range, 9–69 months). Two patients developed interstitial pneumonitis. v. 2-Chlorodeoxyadenosine (2-CdA) 2-CdA was given to 10 ISM, 3 ASM, and 13 SM-AHNMD patients; the drug was used as first-line therapy in 8 patients. CR, MR and PR were achieved in 1, 7, and 4 patients, respectively (ORR=46%). ORR in ISM, ASM, and SM-AHNMD was 50%, 33%, and 46%, respectively. Median duration of response was 11 months (range, 3–74 months). Presence of leukocytosis (WBC > 10 x 109/L), monocytosis (absolute monocyte count > 0.9 x 109/L) or circulating immature myeloid cells was significantly associated with inferior response; 13% vs. 61% (p=0.02); 11% vs. 69% (p=0.006) and 0% vs. 71%, (p=0.001), respectively. Response was not affected by BM detection of KITD816V (p=1.0).Conclusions: Both IFN-a and 2-CdA are reasonable treatment options, with comparable efficacy, for symptomatic SM including the subcategories of ISM, ASM and SM-AHNMD. IFN-a response was significantly better in the absence of anemia or elevated ESR. 2-CdA response was similarly better in the absence of leukocytosis, monocytosis or circulating immature myeloid cells. The therapeutic value of IM was limited to FIP1L1-PDGFRA-positive disease.

Dexamethasone-induced immunosuppression: a rabbit model

Rabbits are often used as animal models for experimental purposes; in many cases steroid-induced immunosuppression is necessary. The aim of this study was to characterise a model of immunosuppression in rabbits, based on changes in the lymphocyte subset distribution, changes in proliferative capacity of lymphocytes and activity of neutrophils 1, 3 and 7 days after the administration of 2 mg/kg dexamethasone phosphate (DXP) three times at 6-h intervals. In peripheral blood, neutrophilia and lymphopenia together with eosinopenia, monocytopenia and basopenia in the absence of leukocytosis was detected. One day after DXP administration the absolute numbers of all lymphocyte subsets decreased in the blood, whereas in bone marrow, absolute numbers of all lymphocyte subsets increased significantly, except CD79α + cells that increased only in relative numbers. The effect of DXP on lymphocytes from the spleen, mesenteric and popliteal lymph nodes was less pronounced. In the thymus, DXP led to a marked reduction of the relative and absolute numbers of CD4 +CD8 + thymocytes. The proliferative capacity of lymphocytes after concanavalin A stimulation was lower in the peripheral blood and spleen only on day 1, no changes were detected in lymph nodes or in bone marrow. A marked increase in proliferative capacity was detected in the thymus. Spontaneous production of reactive oxygen metabolites by neutrophils was reduced on days 1 and 3 after DXP administration. The present results demonstrate clearly that this DXP application protocol is useful for the experimental induction of relatively short-lasting immunosuppression in rabbits.

A souvenir from the Canary Islands

In April, 2004, a previously fi t 67-year-old retired surgeon was referred to our clinic with fever and malaise. Between January and March, 2004, he had holidayed in the Canary Islands. His diet had included cheese, fresh vegetables, salads, fi sh, and wine. At the end of his vacation he experienced lumbosacral pain, which was treated by acupuncture when he returned to Germany. On the last day of treatment he developed fever of 40°C, associated with mild nausea, headache, and myalgia. His general practitioner noted fever, absence of leucocytosis, and a high concentration of C-reactive protein (CRP) of 74 mg/L (normal <5 mg/L). He was treated with roxithromycin for 9 days. Ofl oxacin was added when there was no improvement of his symptoms. Since he remained unwell, his general practitioner referred the patient to us. On presentation to our clinic, physical examination was unremarkable. Blood tests showed a slightly high leucocyte count (12·8×109/L), CRP (81 mg/L), and ESR (106 mm/h). Results of liver function tests were abnormal: alanine aminotransferase 112 IU/L (normal <45 IU/L); aspartate aminotransferase 91 IU/L (normal <50 IU/L); γ-glutamyl transpeptidase 67 IU/L (normal <55 IU/L); and alkaline phophatase 137 IU/L (normal <129 IU/L); but bilirubin was normal. The patient’s activated partial thromboplastin time (APTT) was prolonged at 71 s (normal 26–40 s), but prothrombin time and bleeding time were normal. Anticardiolipin antibodies were high (58 kU/L; normal <10 kU/L). Several blood cultures and examination of bone marrow and cerebrospinal fl uid gave no indication of an infectious agent; serological tests for Q fever were also negative. Abdominal ultrasonography, CT of the head, thorax, and abdomen, transoesophageal echocardiography, and MRI of the spine were also unhelpful. Our patient fulfi lled the Petersdorf criteria for fever of unknown origin (FUO). Although his liver enzyme measurements improved during the fi rst week of admission, we thought liver biopsy would be prudent; doughnut granulomas with a fi brin ring were seen (fi gure). A second serological test for Q fever 2 weeks later was positive for phase II antigens of Coxiella burnetii (IgG 470 kIU/L, normal <50 kIU/L; IgM positive; ELISA assay for IgG and IgM, Serion, Wurzburg, Germany). A diagnosis of acute Q fever infection with hepatic involvement was made. Treatment with doxycycline 200 mg daily for 14 days was initiated but the fever persisted. PCR for C burnetii was negative. A reducing dose of prednisolone 40 mg, 20 mg, and 10 mg daily, each for 48 h was introduced. It resulted in a prompt defervescence and resolution of symptoms within 24 h. During the subsequent weeks, the patient’s liver enzyme measurements, APTT, and anticardiolipin antibodies returned to normal, and in August, 2005, he was still doing well. Hepatic involvement of Q fever is not as common as pneumonia; however, in Spain and the Canary Islands, Q fever often results in liver involvement. In our case, the agent was probably contracted by consumption of cheese made from sheep’s milk; hepatic involvement was probably an autoimmune triggered process. The absence of C burnetii on PCR and the presence of the characteristic granulomas in the liver biopsy sample supports the autoimmune hypothesis, although we cannot exclude the possibility that the negative PCR was due to previous antibiotic treatment. This case highlights the importance of considering Q fever in patients with FUO returning from Spain and the Canary Islands. Q fever should not be excluded if initial serology is negative; liver biopsy can be helpful in these patients, and should be considered in those with abnormal liver function. Furthermore, in Q feverhepatitis, steroids should be added to treatment with doxycycline if clinical symptoms do not improve.

Estudio comparativo de los factores de riesgo y pronósticos de mortalidad en las bacteriemias-fungemias polimicrobianas de un hospital universitario: evolución en 10 años

Eighty-two episodes of polymicrobial bacteremia in two time periods, 1986-87 and 1996-97, were compared to assess differences in risk factors and outcome to mortality. A prospective, concurrent, anterograde study with univariate analysis of all episodes of polymicrobial bacteremia was performed in Hospital de la Princesa. Logistic regression analysis was applied to all significant variables (p < 0.05) in the univariate analysis in either of the two time periods. Variables showing statistically significant differences in incidence between the two time periods included the following: hospital acquired bacteremia; previous use of antibiotics; genitourinary, respiratory and cardiovascular manipulations; septic metastases; and absence of leukocytosis. These factors were more frequently present during 1986-87 than during 1996-97. The overall RR of outcome to mortality was five-fold greater during the first period than the second: RR 5.6 (CI 1.76-17.56) p < 0.001. The clinical characteristics at the onset of bacteremia associated with mortality in the first period were: underlying disease - < RR 2.20 (CI 1.18-4.08), steroid treatment - < RR 4.24 (CI 0.68-26.59), hypotension - < RR 2.05 (CI 1.0-4.17), and disseminated intravascular coagulation - < RR 2.31 (CI 1.69-3.35). Clinical characteristics at the onset of bacteremia associated with mortality in the second period were: hypotension - < RR 1.44 (CI 1.01-2.08), underlying disease - < RR 1.16 (CI 1.02-1.34), and disseminated intravascular coagulation - < RR 6.40 (CI 1.15-35.69). The variables independently associated with mortality in polymicrobial bacteremia were: period - < RR 2.05 (CI 1.50-2.10), underlying disease - < RR 7.05 (CI 2.68-7.50), hypotension - < RR 7.06 (CI 3.80-7.29), and (probably) vascular manipulations - < RR 3.41 (CI 0.85-4.53). Polymicrobial bacteremia-associated mortality was five-fold greater in 1986-87 than in 1996-97. The variables independently associated with mortality risk were underlying disease, hypotension, the period studied (which would include a number of variables not analyzed in this work) and, probably, vascular manipulations.