Does prostate volume correlate with vitamin D deficiency among men undergoing prostate biopsy?

OBJECTIVES: Recent studies demonstrate vitamin D is inversely correlated with BPH and prostate cancer (PCa) incidence. We aim to clarify the associations of vitamin D with prostate volume. METHODS: This is an observational study investigating the associations of serum PSA, PSA density and prostate volume with serum 25-hydroxyvitamin D (25-OH D) in PCa patients and men with negative biopsies seen in outpatient urology clinics in Chicago, IL, USA. There were 571 men (40-79 years old) with elevated PSA or abnormal digital rectal examination with available prostate volume recorded from initial biopsy. The primary outcomes were the unadjusted associations of serum 25-OH D deficiency with prostate volume. The secondary outcomes were the adjusted associations using linear and logistic regression analysis. RESULTS: On univariate analysis, serum 25-OH D<20 ng ml-1 inversely correlated with prostate volume among all men undergoing transrectal ultrasonography (P=0.02), and this relationship remained significant for men with negative biopsy on stratified analysis. In adjusted models, controlling for age, serum PSA, 5-α reductase inhibitors use, obesity and PCa diagnosis, prostate volume was inversely associated with vitamin D (P<0.05) using serum vitamin D as a continuous and categorical variable. Logistic regression model also demonstrated an inverse association between vitamin D (continuous and categorical) and prostate volume ⩾40 grams. CONCLUSION: Serum 25-OH D levels are inversely associated with overall prostate volume and enlarged prostate gland (⩾40 grams), especially in men with benign prostatic disease. Given the largely non-toxic effect of supplementation, consideration should be given to assessing vitamin D levels in men with benign prostatic disease in addition, to malignant prostatic disease.

Emergent role of the fractalkine axis in dissemination of peritoneal metastasis from epithelial ovarian carcinoma.

Epithelial ovarian carcinoma is the most common cause of death from gynecologic cancers largely due to advanced, relapsed and chemotherapy-resistant peritoneal metastasis, which is refractory to the currently used treatment approaches. Mechanisms supporting advanced and relapsed peritoneal metastasis are largely unknown, precluding development of more effective targeted therapies. In this study, we investigated the function of a potentially targetable fractalkine axis in the formation and the development of advanced and relapsed peritoneal metastasis and its impact on patients' outcomes. Our mouse model studies support a role for the fractalkine receptor (CX3CR1) in the initiation of peritoneal adhesion important for recolonization of relapsed peritoneal metastasis. We show that downregulation of CX3CR1 results in reduction of metastatic burden at several peritoneal sites commonly colonized by advanced and relapsed metastatic ovarian carcinoma. We show that the chemokine fractalkine (CX3CL1), an activating ligand of CX3CR1, regulates organ-specific peritoneal colonization. High expression of CX3CR1 correlates with significantly shorter survival, specifically in post-menopausal patients with advanced and terminal stages of the disease. Taken together, our studies support a key regulatory role for the fractalkine axis in advanced and relapsed peritoneal metastasis in epithelial ovarian carcinoma.

Arylsulfatase B (N-acetylgalactosamine-4-sulfatase): potential role as a biomarker in prostate cancer.

BACKGROUND: The enzyme arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) degrades chondroitin-4-sulfate (C4S) and is reduced in malignant colonic and mammary tissues but has not previously been evaluated in prostate cancer. METHODS: ARSB immunostaining was performed on two tissue microarrays (TMAs) and analyzed by digital image analysis, generating ARSB H-scores for prevalence and intensity of epithelial, stromal and combined epithelial and stromal immunostaining. Also, paired malignant and normal prostate tissues were analyzed for ARSB activity, C4S, total sulfated glycosaminoglycans and versican content. The quantities of C4S and of the epidermal growth factor receptor (EGFR) that co-immunoprecipitated with versican were determined in the normal and malignant paired prostate tissues. RESULTS: Forty-four cases of prostate cancer were paired by age (± 5 years), race, Gleason score (in order) and pathological TNM (tumor, node, metastasis) score. The pairs differed by recurrence vs non-recurrence of elevated PSA at ≥ 4 years. When TMA cores were analyzed for ARSB H-score, 18 of the 22 pairs had lower ARSB H-scores in the recurrent member of the pair, whereas higher initial PSA values were associated with recurrence in only 65% of the paired cases. In a second TMA, Gleason scores 6 and 7 were associated with higher ARSB H-scores than Gleason scores 8 and 9 for stroma, epithelium and stroma and epithelium combined (P=0.052, P=0.015, P<0.0001, respectively) and were inversely correlated (r=-0.98, -0.97 and -0.99, respectively). In other paired normal and malignant prostate tissues, ARSB activity was significantly higher in the normal tissues, and C4S and versican values were lower (P<0.0001). C4S that co-immunoprecipitated with versican was greater in the malignant than in the normal tissue, whereas total EGFR that co-immunoprecipitated with versican was reduced. CONCLUSIONS: Study findings suggest that ARSB may be useful as a prognostic biomarker in prostate cancer and that the biological action of ARSB on chondroitin sulfate may impact upon versican's effects in the tumor microenvironment.

Label-free characterization of cancer-activated fibroblasts using infrared spectroscopic imaging.

Glandular tumors arising in epithelial cells comprise the majority of solid human cancers. Glands are supported by stroma, which is activated in the proximity of a tumor. Activated stroma is often characterized by the molecular expression of α-smooth muscle actin (α-SMA) within fibroblasts. However, the precise spatial and temporal evolution of chemical changes in fibroblasts upon epithelial tumor signaling is poorly understood. Here we report a label-free method to characterize fibroblast changes by using Fourier transform infrared spectroscopic imaging and comparing spectra with α-SMA expression in primary normal human fibroblasts. We recorded the fibroblast activation process by spectroscopic imaging using increasingly tissue-like conditions: 1), stimulation with the growth factor TGFß1; 2), coculture with MCF-7 human breast cancerous epithelial cells in Transwell coculture; and 3), coculture with MCF-7 in three-dimensional cell culture. Finally, we compared the spectral signatures of stromal transformation with normal and malignant human breast tissue biopsies. The results indicate that this approach reveals temporally complex spectral changes and thus provides a richer assessment than simple molecular imaging based on α-SMA expression. Some changes are conserved across culture conditions and in human tissue, providing a label-free method to monitor stromal transformations.

Practical aspects of planning, building, and interpreting tissue microarrays: the Cooperative Prostate Cancer Tissue Resource experience.

This is a review of several new approaches developed at or adopted by the Cooperative Prostate Cancer Tissue Resource (CPCTR) to resolve issues involved in tissue microarray (TMA) construction and use. CPCTR developed the first needle biopsy TMA, allowing researchers to obtain 200 or more consecutive cancer sections from a single biopsy core. Using radiographs of original paraffin blocks to measure tissue thickness we developed a method to produce TMAs with a larger number of usable sections. The modular approach to plan TMA construction is also a novel concept wherein TMAs of different types, such as tumor grade TMAs, metastasis TMA and hormone refractory tumors TMA can be combined to form an ensemble of TMAs with expanded research utility, such as support for tumor progression studies. We also implemented an open access TMA Data Exchange Specification that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. It ensures inter-laboratory reproducibility because it offers information describing the preparation of TMA blocks and slides. There are many important aspects that may be missed by both beginners and experienced investigators in areas of TMA experimental design, human subjects protection, population sample size, selection of tumor areas to sample, strategies for saving tissues, choice of antibodies for immunohistochemistry, and TMA data management.

Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung.

BACKGROUND: The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS: In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients with primary adenocarcinoma of the lung. RESULTS: K-ras mutations were detected in the primary tumor using an allele-specific ligation assay. Ninety-two of the 106 patients (87%) with lung adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K-ras mutations were detected in 40 of 106 tumors (38%) and were significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS: The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy.

Antigenic characterization of medullary carcinoma of the breast: HLA-DR expression in lymph node positive cases.

Medullary carcinoma of the breast has attracted attention because of its relatively good prognosis, in spite of its high cytologic grade. It has, by definition, a consistent, florid tumor infiltrating lymphocyte (TIL) population, probably the result of cytotoxic T-lymphocytes recognizing tumor cells in an HLA-DR-restricted manner. HLA-DR tends to be more highly expressed on primary medullary carcinoma cells than on ductal carcinoma cells; however, the MHC-class II antigenicity of the tumor cells themselves has not been analyzed extensively, and as yet there has been no comparative study of HLA-DR expression in medullary and ductal carcinomas metastatic to lymph nodes. Eleven cases of medullary carcinoma and 15 cases of ductal carcinoma, primaries, and respective lymph node metastases were analyzed by immunoperoxidase staining for HLA-DR and lymphocytes antigens. Polymerase chain reaction (PCR) analysis to identify HLA-DR subtypes from the paraffin blocks was performed on selected cases of primaries and nodal metastases of both tumor types. Immunoperoxidase staining for HLA-DR antigen revealed a marked difference in antigen expression between medullary and ductal carcinomas. In the medullary carcinomas, the mean percentage of cells staining for HLA-DR was 74.5% in the primary tumors and 67.3% in the nodal metastases. For the ductal carcinomas, the mean percentage of cells staining was 17.7% in the primaries and 7% in the metastases. There was a tendency for the level of HLA-DR expression to remain high in medullary carcinoma metastatic to nodes, whereas whatever HLA-DR was present within ductal primaries tended to diminish when cells metastasized to regional nodes. PCR analysis of the HLA-DR within the two tumor types revealed no emerging subtype or variant that could be associated with either the medullary or the ductal carcinomas. Medullary carcinoma cells express much greater quantities of HLA-DR, on the whole, than ductal carcinomas. Expression of HLA-DR is retained on medullary carcinoma cells that have spread to lymph nodes, whereas the smaller quantities of HLA-DR present within ductal primaries tend to diminish even further when the tumor cells are found in lymph nodes. No discernible HLA-DR mutations or predominant subtypes emerged on PCR analysis, and the authors therefore conclude that it is the quantity and not the quality of HLA-DR expression in medullary carcinoma that maintains the characteristic TIL infiltrate, not seen in ductal carcinomas.

Laryngotracheal reconstruction in canines: fixation of autologous costochondral grafts using polylactic and polyglycolic acid miniplates.

OBJECTIVE: To examine the feasibility of a new method of laryngotracheal reconstruction (LTR) that uses a bioabsorbable plating system consisting of polylactic and polyglycolic acid and provides some advantages over currently used methods. DESIGN AND INTERVENTIONS: Anterior subglottic stenosis was created in 10 beagles that then underwent LTR using an autologous costochondral graft. External laryngotracheal framework and cartilage grafts were secured using a sheet and screws made from a copolymer composed of polylactic and polyglycolic acid. Animals were humanely killed at 40, 60, and 90 days, and specimens were submitted for pathological examination. Histologic analysis included evaluation for inflammatory reaction, polylactic and polyglycolic acid incorporation into cartilage, cartilage necrosis, cartilage remodeling, and graft epithelialization. RESULTS: All animals underwent LTR after creation of a subglottic stenosis without episodes of airway compromise. After LTR, all airways were returned to prestenosis diameter without significant complication, and all animals were immediately extubated after surgery without difficulty. After the animals were killed, distraction of the stenotic cricoid area was demonstrated in 100% of the cases. Significant necrosis was noted in 2 of 10 grafts grossly; however, histologic analysis demonstrated significant areas of viable cartilage, areas of cartilage remodeling, and good epithelialization despite graft necrosis. Complete epithelialization of grafts was noted in the other 8 specimens. CONCLUSIONS: Using a canine model, we demonstrated a bioabsorbable plating system that offers an effective method for LTR. This model has the advantages of providing external support to the operated laryngeal and tracheal framework, elimination of the difficulties of suture placement, and potential future failure while offering rigid external fixation of a cartilage graft.

Methods of cytologic smear preparation and fixation. Effect on the immunoreactivity of commonly used anticytokeratin antibody AE1/AE3.

OBJECTIVE: To evaluate the effect of fixation and methods of cytologic smear preparation on the immunoreactivity of commonly used anticytokeratin antibody AE1/AE3. STUDY DESIGN: Scrape cytology smears and formalin-fixed, paraffin-embedded tissue sections (FPTS) of 20 unfixed, fresh specimens submitted for intraoperative consultation were studied by the immunoperoxidase method. In addition to the morphologic examination, the smears and FPTS were evaluated for intensity and proportion scores. For each specimen, two scrape cytology smears were wet fixed in 95% ethanol, and 12 smears were air dried without fixation. Air-dried smears were either postfixed after rehydration in saline or fixed directly without rehydration by one of the three fixatives: alcoholic formalin, 95% ethanol with 5% acetic acid or 95% ethanol. RESULTS: Both intensity and proportion scores were higher with rehydrated, air-dried smears as compared to those without rehydration and were comparable to those with wet-fixed smears and FPTS. In the rehydrated group, the optimum results were achieved when the smears were postfixed with alcoholic formalin. CONCLUSION: The method of preparation and fixation had variable effects on the immunoreactivity of anticytokeratin antibody AE1/AE3. The optimum results were achieved with saline-rehydrated, air-dried smears post-fixed in alcoholic formalin. To evaluate the role of inter-sample variation, further, larger studies are recommended on this and other antibodies before applying them to different types of cytologic smears.

Cervical cytology and immunohistochemical features in endometrial adenocarcinoma simulating microglandular hyperplasia. A case report.

BACKGROUND: The histology of a few cases of adenocarcinoma simulating cervical microglandular hyperplasia (MGH-AdCa) has been reported. However, the cytologic features of MGH-AdCa in cervical smears and the immunohistochemical profile have not been described. CASE: A 73-year-old female presented with vaginal bleeding. The cervical Pap smear was initially interpreted by the cytotechnologist as "reactive endocervical cells" and was referred for cytopathologist review. The final interpretation was atypical glandular cells of undetermined significance (AGUS), probably neoplastic. Endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy showed International Federation of Gynecologists and Obstetricians grade 1 endometrial carcinoma. The superficial component of the tumor resembled cervical microglandular hyperplasia (MGH); the deeper component had an endometrioid pattern. The Pap smear predominantly showed a glandular component with features of MGH. However, the presence of scattered single cells with hyperchromatic nuclei, one to three nucleoli, easily detectable mitotic figures, randomly scattered apoptotic bodies and focal, watery diathesis suggested a neoplastic process. Immunohistochemistry was studied on paraffin sections. In addition to other markers, the tumor cells were immunoreactive for carcinoembryonic antigen (CEA). CONCLUSION: Although the cervical Pap smear in this case had an MGH-like pattern, some features were atypical enough to suggest a diagnosis of AGUS, probably neoplastic. CEA immunoreactivity of MGH-AdCa could also help to differentiate it from MGH.

Metalloproteinase levels are decreased in symptomatic carotid plaques.

BACKGROUND: Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic plaques, but their role in the development of clinical symptoms remains ill defined. We correlated the activity and levels of metalloproteinase enzymes and their inhibitors in human carotid plaques to ischemic neurologic events. METHODS: Carotid plaques were collected at the time of endarterectomy from 23 patients with carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA assay. Macrophage accumulation in the plaque was determined using immunohistochemistry. RESULTS: Plaques from symptomatic patients had decreased proteolytic activity on substrate gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9). A decrease in pro-MMP-9 (8.21 +/- 2.35 vs 17.42 +/- 3.14 ng, P < 0. 05) and an increase in TIMP-2 protein (12.62 +/- 0.58 vs 10.56 +/- 0. 77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was noted in macrophage accumulation in the plaques between the two groups. CONCLUSIONS: Plaques from patients who present with ischemic neurologic symptoms have decreased proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein levels. These data suggest that metalloproteinase enzymes are not responsible for plaque instability in the carotid circulation and may in fact promote plaque stability.

The role of constitutive NF-kappaB activity in PC-3 human prostate cancer cell invasive behavior.

The purpose of this study was to determine if increased NF-kappaB activity of highly invasive PC-3 cells contributed to their invasive behavior. Increased NF-kappaB activity has been observed in several malignant tumors and it may have an important role in tumorigenesis, progression and chemotherapy resistance. By serial selection, we obtained invasion variant PC-3 cell sublines. The PC-3 High Invasive cells invade readily through a Matrigel reconstituted basement membrane while PC-3 Low Invasive cells have low baseline invasion activity. In these studies, we discovered that NF-kappaB DNA binding activity was increased in PC-3 High Invasive cells when compared to PC-3 Low Invasive cells by electrophoretic mobility shift assay (EMSA). Gel supershift assays showed a 4-fold increase in p65 containing complexes and a 2.2-fold increase in the p50 containing complexes in the PC-3 High Invasive cells. Luciferase reporter assays showed that NF-kappaB dependent transcription activity was increased 10.2 +/- 2.5-fold in the highly invasive cells (P < 0.002). The PC-3 High Invasive cells showed a constitutive increase in phospho-IkappaB alpha and introduction of the super-repressor IkappaB alpha S32/36A inhibited NF-kappaB activity to 19.2 +/- 2.5 percent of control transfected cells (P < or = 0.001). The IkappaBa super-repressor reduced the basement membrane invasion of PC-3 High Invasive cells from 6.2 +/- 1.1 to 3.8 +/- 0.4 percent (P < 0.002) with no decrease in cell viability or proliferation. These results demonstrate that increased NF-kappaB activity contributed directly to the invasive behavior of PC-3 High Invasive prostate cancer cells.

Prostate-specific antigen expression and lipochrome pigment granules in the differential diagnosis of prostatic adenocarcinoma versus seminal vesicle-ejaculatory duct epithelium.

BACKGROUND: Lipochrome pigment granules (LPGs) and prostate-specific antigen (PSA) localization have been cited as helpful adjuncts in differentiating atypical histologic patterns of seminal vesicle-ejaculatory duct (SVED) from prostatic adenocarcinoma. However, LPGs have been described in both benign and neoplastic prostatic acini, and PSA expression within the intraprostatic SVED has not been fully explored. DESIGN: Fifty radical prostatectomy specimens were studied for LPGs and 9 cases for PSA expression. RESULTS: Two morphologic types of LPGs (type 1 and type 2) were observed. The reproducibility in classifying LPGs was evaluated by kappa statistics, which demonstrated a strong agreement between 4 observers. Type 1 was restricted to SVED in all 50 specimens. Type 2 was subclassified into 2A and 2B. Type 2 LPGs were observed in prostatic acini of different zones, high-grade prostatic intraepithelial neoplasia, prostatic adenocarcinoma, and occasionally with type 1 LPG in SVED. Focal reactivity for PSA in the distal portion of SVED near urethra was noted in 1 of 9 cases. CONCLUSION: Awareness about morphologic differences between the 2 types of LPGs could help to avoid a potential diagnostic pitfall of misinterpreting SVED epithelium for adenocarcinoma. Caution is recommended in interpreting PSA expression, since rare focal PSA reactivity was observed in the distal SVED.

Primary ocular Epstein-Barr virus-associated non-Hodgkin's lymphoma in a patient with AIDS: a clinicopathologic report.

OBJECTIVE: To report an unusual case of chronic multifocal chorioretinitis with vitritis in a patient with acquired immunodeficiency syndrome (AIDS) that was resistant to antiviral and antitoxoplasmic medication and required a retinal biopsy for definitive diagnosis. METHODS: Vitreous biopsy, pars plana vitrectomy, and retinal biopsy were performed. The vitreous biopsy material was sent for bacterial, fungal, and viral culture, and the vitreous cassette was sent for cytology. The retinal biopsy material was divided and sent for polymerase chain reaction testing for toxoplasmosis and virology and pathologic tissue analysis. RESULTS: Vitreous cytology showed a mixed population of lymphocytes and histiocytes, but all other microbiologic and virologic studies were negative. Tissue analysis revealed an infiltrate of atypical mononuclear cells extending from the inner limiting membrane through the outer plexiform layer characteristic of a B cell, non-Hodgkin's lymphoma of the central nervous system (NHL-CNS). In situ hybridization for the Epstein-Barr virus (EBV) was positive. An extensive systemic evaluation did not show evidence of extraocular tumor. CONCLUSION: Although rare, primary ocular NHL-CNS can be seen in patients with AIDS, and its clinical presentation often closely resembles other disorders. To our knowledge, this case represents the first ocular NHL in which EBV is shown to be associated.

In vitro and in vivo MR imaging of hyaline cartilage: zonal anatomy, imaging pitfalls, and pathologic conditions.

Hyaline cartilage plays an essential role in the maintenance of normal synovial joint function by reducing friction and distributing loads. Histologic analysis of hyaline cartilage reveals zonal variation in cellular morphology, proteoglycan concentration, and collagen fiber size and orientation. High-resolution magnetic resonance (MR) imaging reveals an analogous laminar anatomy that is often visible on clinical images obtained with proper attention to technique. In vitro and in vivo pulse sequences show three distinct laminae: a hypointense superficial lamina, a hyperintense intermediate lamina, and a heterogeneous deep lamina that consists of alternating hyperintense and hypointense bands perpendicular to the subchondral bone. Imaging pitfalls include magic angle effects, truncation artifact, partial volume effect, regional anatomic variation, chemical shift, and magnetic susceptibility effects. Pathologic conditions that affect articular cartilage include chondromalacia patellae, osteoarthritis, and localized traumatic lesions. Although detection of early cartilage disease remains elusive, MR imaging can demonstrate intermediate and advanced lesions.

Identification of heavy drinkers using a combination of laboratory tests.

OBJECTIVE: This study derived and evaluated a model that used results of commonly performed laboratory tests to identify men who are heavy drinkers. METHOD: The results of 40 commonly available laboratory tests were obtained on a diverse sample of 426 heavy drinkers and 188 light drinkers. A logistic regression equation for identifying heavy drinkers was derived in a training data set of 411 subjects and tested in a validation data set of 203 subjects. RESULTS: Ten laboratory measurements were included in the final regression equation: chloride, sodium, ratio of direct to total bilirubin level, blood urea nitrogen, high density lipoproteins, monocyte count, phosphorus, platelets, aspartate aminotransferase, and mean corpuscular hemoglobin. In the validation data this model correctly identified 98% of the 161 heavy drinkers and 95% of the 42 light drinkers. Other models reported in previous literature were applied to these subjects and did not perform as well. The model performed better for subjects of lower socioeconomic status. CONCLUSIONS: The laboratory tests in our model may help identify heavy drinkers. The performance of models to identify heavy drinkers depends on the demographic characteristics of the subjects.

Antimicrobial effect on rabbit sinusitis after temporary ostial occlusion.

A key precipitating factor in the pathogenesis of acute bacterial sinusitis (ABS) is ostiomeatal obstruction. It has been postulated that ABS cannot resolve until the sinus ostium is patent. The primary purpose of this study is to quantify sinusitis resolution after temporary ostial occlusion in a rabbit model. A secondary aim is to quantify bacterial clearance with and without antimicrobial therapy in Staphylococcus aureus infected sinuses. A blinded, placebo controlled study in 10 New Zealand white rabbits was performed using Merocel as a temporary maxillary sinus ostial obstruction. Computerized tomography (CT) of the maxillary sinuses was obtained before and after bilateral ostial occlusion; sinuses were cultured and then the left sinus was injected with approximately 10(8) cfu/mL S. aureus. CT imaging and sinus cultures were obtained and then the ostial plugs were removed. Serial CT and cultures were done until sinusitis resolved and cultures were negative for S. aureus. Mean CT sinusitis scores increased with ostial obstruction and decreased with ostial plug removal (P < 0.0001 and P < 0.001). Injection of S. aureus did not significantly change mean CT sinusitis scores despite being cultured from 45% of sinuses. Antimicrobial therapy was not significant in reducing mean CT scan sinusitis scores or positive cultures. Resolution of mucosal swelling is more dependent on relief of ostial obstruction rather than antimicrobial therapy in this rabbit model.

Characterization of normal and malignant human hepatocytes by Raman microspectroscopy.

Raman microspectroscopy was used to characterize normal and malignant hepatocytes in both cultured cells and human liver tissues. Consistent spectral changes were observed, including intensity increases at 1040 and 1083 cm(-1) with malignancy. A loss of intensity at 1241 cm(-1) was also observed in cancer cells, but was obscured in tissues by the overlap of a 1253 cm(-1) band, thought to originate from heme proteins. Normal liver tissue also differed from both the malignant tumor and its accompanying cirrhotic tissue at 1182 cm(-1). These results demonstrate the potential usefulness of Raman spectroscopy in clinical diagnosis, and investigations into the source of the observed spectral changes will provide information on the underlying mechanisms of carcinogenesis.