The Role of Invasive and Non-Invasive Procedures in Diagnosing Fever of Unknown Origin

Background: The etiology of fever of unknown origin has changed because of the recent advances in and widespread use of invasive and non-invasive diagnostic tools. However, undiagnosed patients still constitute a significant number.Objective: To determine the etiological distribution and role of non-invasive and invasive diagnostic tools in the diagnosis of fever of unknown origin.Materials & Methods: One hundred patients who were hospitalized between June 2001 and 2009 with a fever of unknown origin were included in this study. Clinical and laboratory data were collected from the patients'' medical records retrospectively.Results: Fifty three percent of the patients were male, with a mean age of 45 years. The etiology of fever was determined to be infectious diseases in 26, collagen vascular diseases in 38, neoplastic diseases in 14, miscellaneous in 2 and undiagnosed in 20 patients. When the etiologic distribution was analyzed over time, it was noted that the rate of infectious diseases decreased, whereas the rate of rheumatological and undiagnosed diseases relatively increased because of the advances in imaging and microbiological studies. Seventy patients had a definitive diagnosis, whereas 10 patients had a possible diagnosis. The diagnoses were established based on clinical features and non-invasive tests for 61% of the patients and diagnostic benefit was obtained for 49% of the patients undergoing invasive tests. Biopsy procedures contributed a rate of 42% to diagnoses in patients who received biopsies.Conclusion: Clinical features (such as detailed medical history-taking and physical examination) may contribute to diagnoses, particularly in cases of collagen vascular diseases. Imaging studies exhibit certain pathologies that guide invasive studies. Biopsy procedures contribute greatly to diagnoses, particularly for malignancies and infectious diseases that are not diagnosed by non-invasive procedures.     

Serum IL-8 and IL-12 levels in breast cancer

Interleukins (ILs) are known to play a fundamental role in cancer. We investigated the serum levels of IL-8 and IL-12, in breast cancer patients, and their relationship with the prognostic parameters and therapy. Fortyeight patients with pathologically verified breast carcinoma and 21 healthy controls were enrolled into the study. Serum samples were obtained at baseline and after two cycles of chemotherapy. Serum IL-8 and IL-12 levels were determined using enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the baseline serum IL-8 and IL-12 levels between breast cancer patients and healthy controls (p = 0.365 andp = 0.871, respectively), no significant correlation between the prognostic parameters and the serum IL-8, IL-12 levels. However, in the subgroup consisting of metastatic breast cancer patients, baseline serum IL-8 levels were significantly higher compared with non-metastatic disease (p = 0.047). Anthracycline-based chemotherapy and the addition of taxane did not change the levels of both serum IL-8 and IL-12. Serum IL-8 level may be useful in determining metastatic breast cancer. Larger studies are needed to confirm this finding.     

Malignant mesothelioma of the tunica vaginalis testis: a case report and review of the literature

Most often, mesotheliomas involve the serosal membranes of the pleura and peritoneum. Sometimes, mesothelial proliferations are identified in other locations. A mesothelioma, within the tunica vaginalis of the paratesticular region is rare but often fatal malignancy of the male genitalia. Despite aggressive surgical and systemic therapy the prognosis remains poor with only rare long-term survivors. We report a case of malignant mesothelioma of the tunica vaginalis in 45-years-old and review of the literature is presented.     

Addition of topotecan to standard cisplatin/etoposide combination in patients with extended stage small cell lung carcinoma

BACKGROUND: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell lung cancer (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC. MATERIALS AND METHODS: Twenty-one patients (median age 55 years, and 18 male) with chemotherapy-naive ED-SCLC were enrolled into the study. PET treatment consisted of etoposide 80mg/m(2), cisplatin 20mg/m(2) and topotecan 0.75mg/m(2) and all were given intravenously on days 1 to 3 for every 3 weeks. RESULTS: Leucopoenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Severe leucopenia/neutropenia were observed in 14 (67%)/12 (57%) patients, and only two (10%) developed febrile neutropenia. Severe thrombocytopenia was observed in 6 (29%) patients and one patient died due to orbital and cerebral haemorrhage. Dose reductions were required in 13 (62%) patients, delays in 8 (38%) patients and early treatment discontinuation in 3 (14%) patients. The overall response rate was 52.6% (95% CI: 28, 9-75.6) with 2 (10.5%) complete and 8 (42.1%) partial responses. The overall median survival time was 6.6 months (range 0.5-16.5 months) and the 6-month overall survival was 65.3%+/-11.7. The overall median survival time of responders was 9.7 months compared to 5.7 months in non-responders (p=0.026). CONCLUSION: Topotecan combined with PE regimen with this schedule and dosage does not seem to provide any benefit in terms of response and survival in ED-SCLC patients and does not deserve further studies.     

Increased body mass index is not a reliable marker of good nutrition in hemodialysis patients

OBJECTIVE: The aim of the study was to assess the body fat (BF) composition in hemodialysis (HD) patients using anthropometry and bioelectrical impedance analysis (BIA) and investigate relationships between BIA-determined BF composition and nutritional parameters in different weight groupings. DESIGN: Cross-sectional study. SETTING: A tertiary-care university hospital. METHODS: 164 HD patients (M/F: 89/75, mean age: 48.4 +/- 15.8 years, mean HD duration: 58.2 +/- 42.6 months) were divided into three groups according to body mass index (BMI): normal weight (NW: BMI 18.5-24.9), overweight (OW: BMI 25-29.9), obese (OB, BMI > or = 30). Biochemical parameters and BF composition using anthropometry and foot-to-foot BIA were compared between three groups. RESULTS: Ninety-six (59%) patients were NW, 40 (24%) were OW, and 28 (17%) were OB. Average mean skinfold thickness (p = 0.005), mid-arm circumference (p = 0.001), BF% (p = 0.001), and fat-free mass (FFM) (p = 0.03) were all significantly greater in the OB group than in the NW group. Compared to the NW patients, the OB group had significantly higher serum levels of glucose (p = 0.03), total cholesterol (p = 0.02), and triglycerides (p = 0.02), but significantly lower serum albumin (p = 0.05) and blood urea nitrogen (p = 0.05). The OB group also had significantly higher white blood cell count (p = 0.002) and serum CRP (p = 0.001) than the NW group. CONCLUSIONS: The results suggest that BIA-determined BF composition is correlated with body mass index. In addition, obesity is associated with elevated CRP and white blood cell count and lower serum albumin level in HD patients.     

Autoimmune thrombocytopenia induced by PEG-IFN-alpha plus ribavirin in hepatitis C

Mild thrombocytopenia is a common adverse effect of interferon-alpha and pegylated interferon-alpha, largely ascribed to bone marrow suppression. Nevertheless, rare cases of autoimmune thrombocytopenia following standard or pegylated interferon treatment have been reported in the literature. In this report, we have presented a patient who developed an immune-mediated thrombocytopenia during the course of therapy with pegylated interferon/ribavirin for hepatitis C virus infection. After cessation of pegylated interferon/ribavirin treatment, thrombocytopenia was treated successfully with danazol and intravenous gamma-globulin.     

Neuroprotective effects of infliximab in experimental spinal cord ischemic injury

Reactive oxygen species (ROS) have been implicated in the pathogenesis of spinal cord injury after both ischemia–reperfusion (I/R) and trauma. This experimental study was designed to investigate the potential effects of infliximab, an anti-tumor necrosis factor-α agent, on I/R injury of the rabbit spinal cord. Eighteen New Zealand white rabbits were divided into three groups, each consisting of six rabbits: sham (no I/R), I/R, and infliximab (I/R + infliximab). Spinal cord ischemia was induced by applying an infrarenal aortic cross clamp for 30 minutes. At 48 hours after ischemia, animals were functionally evaluated using the Tarlov score. Changes in the spinal cord were observed by measuring tissue levels of malondialdehyde (MDA), glutathione (GSH), advanced oxidation protein products (AOPP), and superoxide dismutase (SOD) and by evaluating hematoxylin–eosin-stained sections. At 48 hours after ischemia, the Tarlov scores in the infliximab group were higher than those of the I/R group, MDA and AOPP levels in the I/R group were significantly higher than those in the sham and infliximab groups (p < 0.05), and SOD levels in the infliximab group were significantly higher than those in the I/R and sham groups (p < 0.05). The sham group had higher GSH levels than the infliximab group; however, the difference was not statistically significant (p > 0.05). Histological examination revealed that the infliximab group had significantly less vascular proliferation, edema, and neuron loss than the I/R group. These results indicate that infliximab may protect the spinal cord against injury in a rabbit I/R model.     

Limited smoothelin expression within the muscularis mucosae: validation in bladder diverticula

Smoothelin, a marker of differentiated smooth muscle, is diffusely expressed by bladder muscularis propria and is negative to only weakly and focally expressed in muscularis mucosae. We used bladder diverticula, which lack muscularis propria and frequently demonstrate hyperplastic muscularis mucosae, to evaluate the use of smoothelin immunoreactivity in diagnostic pathology. Diverticula from 40 patients (21 with benign features, 19 with neoplastic features) were studied. Immunohistochemistry was performed using smoothelin antibody (clone R4A, 1:150 dilution; Abcam, Cambridge, MA); and tissue was scored as 0 (no expression), 1+ (moderate expression b10% of cells), 2+ expression (moderate expression N10% of cells), and 3+ (robust diffuse expression). All diverticula contained muscularis mucosae of varying caliber; staining in diverticular muscularis mucosae was compared with historic results in the muscularis mucosae of cystectomy specimens. Hyperplastic muscularis mucosae occurred in 31 (78%) of 40 cases. Smoothelin immunoreactivity in the diverticular muscularis mucosae included 0 (16/40, or 40%); 1+ (11/40, or 27.5%); 2+ (13/40, or 32.5%); and 3+ (0/40, or 0%), with a slightly higher 2+ expression level in hyperplastic versus nonhyperplastic muscularis mucosae (35% versus 22%). Adjacent normal muscularis propria, present in 12 specimens, demonstrated 3+ muscularis propria immunoreactivity. Comparison between diverticula with benign and neoplastic features showed no significant difference in smoothelin immunoreactivity. No correlation was evident with smoothelin immunohistochemistry and muscle caliber. Smoothelin immunoreactivity in bladder diverticula confirms the limited nature of smoothelin expression in the muscularis mucosae and represents a useful ancillary technique in the proper histopathologic evaluation of diverticular and nondiverticular bladder carcinomas. A strong and robust staining of smooth, rounded muscle with smoothelin remains a useful diagnostic adjunct in the reliable recognition of muscularis propria.