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Biomedical subjects

B Davidson

Publications and source records attributed to B Davidson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporine-induced renal impairment: a preliminary report.

BACKGROUND: Cyclosporine is the most common maintenance immunosuppressant in liver transplants patients, but it is often associated with nephrotoxicity. METHODS: We evaluated the safety and efficacy of monotherapy with mycophenolate mofetil (1 g twice daily) in five stable liver transplant patients with cyclosporine-induced renal impairment despite reduction of cyclosporine to subtherapeutic levels. Follow-up was 8.4+/-2.4 (range: 6-12) months. RESULTS: No major side effects have been observed to date. Serum creatinine levels were significantly reduced from a median of 201 micromol/L before to 142 micromol/L at 3 months after mycophenolate (P=0.04) and remained low at 6 months. New onset cellular rejection occurred in only one patient after 3 months on mycophenolate monotherapy, and it responded completely to an intravenous course of methylprednisolone. CONCLUSIONS: Monotherapy with mycophenolate mofetil in a dose of 1 g twice daily seems to significantly improve cyclosporine-induced renal impairment in stable liver transplant patients without major side effects or significant risk of rejection.

Creatinine↗
PubMed1999

Increased olfactory sensitivity in first episode psychosis and the effect of neuroleptic treatment on olfactory sensitivity in schizophrenia.

Olfactory sensitivity to two odorants, isoamyl acetate and androstenone, was assessed in 19 male schizophrenic patients and 10 control subjects. Tests were performed during a drug-free period and 2-3 weeks after initiation of neuroleptic drug therapy. Olfactory sensitivity in schizophrenic patients was significantly impaired during the drug-free period and neuroleptic treatment further reduced olfactory sensitivity in these patients. The same olfactory tests were administered to 22 first-episode-psychosis patients, 12 first-episode-schizophrenia and 10 brief-psychotic-disorder patients, as well as to 20 age-matched control subjects. The first-episode-psychosis patients had significantly higher sensitivity to isoamyl acetate and to androstenone, but the incidence of anosmia to androstenone was not higher in the first episode patient group as compared to the control group. We conclude that olfactory dysfunction in schizophrenic patients, and possibly other forms of psychosis, is mainly due to long-term effects of commonly used neuroleptic drugs.

Acute Disease↗
PubMed1999

Changes in tissue oxygenation of the porcine liver measured by near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a novel method for the measurement of tissue oxygenation and may have a role in monitoring liver oxygenation and viability. The aim of this study is to validate the application of NIRS for monitoring hepatic tissue oxygenation. Large Landrace pigs (n = 12) underwent laparotomy and liver exposure. Total hepatic blood flow (THBF) was measured by the Transonic Medical Flowmeter system. NIRS probes were placed on the liver surface to continuously record changes in hepatic tissue oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and the reduction-oxidation state of cytochrome oxidase (Cyt Ox). Reduction of hepatic tissue oxygenation was achieved by hepatic vascular inflow occlusion (n = 6) or reduction of inspired oxygen (FIO2; n = 6). The THBF changes correlated significantly with hepatic HbO2 (r = 0.84; P <.001) and Cyt Ox (r = 0.88; P <.001). With reduction of FIO2, a significant correlation was found between arterial oxygen saturation and hepatic HbO2 and Hb (r = 0.99 and r = -0.99, respectively; P <.0001). NIRS measurement of liver parenchymal oxygenation correlates well with changes in liver blood flow and arterial oxygenation.

Animals↗
PubMed1999

Isolation of human hepatocytes after hepatic warm and cold ischemia: a practical approach using University of Wisconsin solution.

A method is described for isolating human hepatocytes from tissue fragments after warm and cold ischemia as experienced during hepatic resections. Cells with a high trypan blue dye exclusion and good culture characteristics were isolated by employing an initial tissue perfusion with UW solution. The method could facilitate transfer of liver tissues between distant centers for cell isolation studies.

Adenosine↗
PubMed1999

Expression of matrix metalloproteinase-9 in squamous cell carcinoma of the uterine cervix-clinicopathologic study using immunohistochemistry and mRNA in situ hybridization.

OBJECTIVE: Invasion of the extracellular matrix and blood vessels by malignant neoplasms, with subsequent distant dissemination, is a key event in tumor progression. This process appears to be mediated largely through the action of matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells. The role of gelatinases (MMP-2 and MMP-9) in basement membrane and matrix degradation was described in various tumors. We studied MMP-9 protein expression in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma using immunohistochemistry and detected MMP-9 mRNA using in situ hybridization. METHODS: Fifty squamous cell carcinomas, 10 cases of CIN II-III, and 10 normal cervices were stained for MMP-9, using a monoclonal antibody. The presence of MMP-9 mRNA was studied using in situ hybridization. Results were correlated with patient survival during a follow-up period of up to 167 months (average, 41 months). RESULTS: Immunohistochemical staining of tumor cells for MMP-9 was noted in 36/50 (72%) carcinomas and 5/10 (50%) CIN lesions, but was uniformly absent from the nonneoplastic epithelium adjacent to tumors and from control cervices. Peritumoral staining of stromal cells was observed in 27/50 (54%) carcinomas, but only in 3/10 (30%) CIN lesions and 1/10 (10%) control cervices. The presence of MMP-9 mRNA was detected in tumor cells in 39 (78%) carcinomas and 8 (80%) CIN lesions, but only in 4 (40%) control cervices. An intense signal for MMP-9 mRNA was observed most frequently in carcinomas. MMP-9 mRNA was detected in stromal cells in the majority of cases. However, an intense signal was observed only in stromal cells around invasive tumors. In survival analysis, age (P = 0.016), grade (P = 0. 016), and stage (P = 0.001) showed independent correlation with poor survival. Neither MMP-9 protein expression nor an intense signal for MMP-9 mRNA was associated with poor survival, although the latter was observed more frequently in neoplastic cells of lethal tumors (8/14 tumors vs 11/36 nonlethal tumors). CONCLUSIONS: MMP-9 mRNA and protein expression are elevated in tumor and stromal cells of both high-grade CIN and invasive squamous cell carcinoma of the uterine cervix. Thus, MMP-9 is possibly an early marker of tumor progression in squamous lesions of the cervix. An intense stromal signal for MMP-9 mRNA characterizes some invasive carcinomas. Expression of MMP-9 in cervical carcinoma cells is present in both lethal and nonlethal tumors, consistent with the key role of this proteolytic enzyme in invasion, and does not appear to predict disease outcome.

Adult↗
PubMed1999

MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma--a clinicopathologic study using immunohistochemistry and mRNA in situ hybridization.

OBJECTIVE: The spread of malignant neoplasms is closely associated with matrix and basement membrane degradation, mediated by various classes of proteolytic enzymes. Matrix metalloproteinases (MMP) appear to have a key role in the sequence of events that lead to local invasion and metastasis. The present study evaluated the role of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-2 (TIMP-2), and membrane-type metalloproteinase (MT1-MMP) in cervical neoplasia. METHODS: We have analyzed 49 uterine cervical squamous cell carcinomas, 10 cases of high-grade cervical intraepithelial neoplasia (CIN II-III), and 10 control cervices for the presence of MMP-2, TIMP-2, and MT1-MMP using in situ hybridization. MMP-2 protein expression was evaluated using immunohistochemistry. Results were analyzed for possible correlation with disease outcome. RESULTS: MMP-2, TIMP-2, and MT1-MMP mRNA were localized to both stromal and tumor cells. However, an intense signal for MMP-2 was detected almost exclusively in tumor cells and was uniformly absent from CIN lesions and control cervices. Conversely, intense signals for TIMP-2 and MT1-MMP were detected in both stromal and tumor cells of invasive carcinomas, more often for the former. As with MMP-2, they were absent from CIN lesions. MMP-2 protein expression was enhanced in tumor cells compared to CIN cases and controls, significantly compared to the latter (P = 0.01). The presence of both MMP-2 and TIMP-2 mRNA in tumor cells correlated with advanced stage (P = 0.003 for MMP-2, P = 0.002 for TIMP-2) and with poor survival (P = 0.003 for MMP-2, P = 0.002 for TIMP-2) in univariate analysis. In addition, their presence in tumor cells intercorrelated (P = 0.002). In multivariate survival analysis, MMP-2 presence retained its association with survival (P = 0.004), in addition to patient age (P = 0.027) and advanced stage (P = 0. 0002). CONCLUSIONS: Both MMP-2 and TIMP-2 have a key role in extracellular matrix invasion in cervical carcinoma, largely through their elaboration by tumor cells. The presence of mRNA for both proteins is interrelated and is associated with poor survival.

Adult↗
PubMed1999

Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers.

The detection of malignant cells in pleural, peritoneal, and pericardial fluids of cancer patients marks the presence of metastatic disease and is associated with a grave prognosis. We evaluated five epithelial markers for the detection of cancer cells in 94 fresh pleural, peritoneal and pericardial effusions. Eighty-four of the samples were regarded as adequate for analysis after evaluation of cytological smears, including 61 samples from patients known to have gynaecological neoplasms. The other 23 samples were from patients with various non-gynaecological malignancies or tumours of unknown origin. Our control cases were 10 fallopian tubes not affected by any malignancy and 12 malignant mesotheliomas. Cell blocks from all cases were stained for CA-125, BerEP4, carcinoembryonic antigen (CEA), BG8 (Lewis Y blood antigen), and B72.3 (TAG-72). Fifty-one of 84 cases were diagnosed as malignant or suggestive of malignancy in cytological smears and/or cell block sections. However, staining for epithelial markers highlighted the presence of malignant cells in 7 additional cases. When membrane staining was evaluated, the sensitivity of the markers studied in detecting malignant cells was as follows: CA-125: 88%, BerEP4: 78%, CEA: 26%, BG8: 86%, B72.3: 79%. Membrane positivity for CEA, B72.3 and BerEP4 was not detected in reactive mesothelial cells. However, membranous staining in mesothelial cells was evident in 13% and 31% of cases with the use of BG8 and CA-125, respectively. Weak cytoplasmic staining for CEA was observed in mesothelial cells in 2 cases. When Ber-EP4, B72.3, and BG8 staining results in cancer cells were combined, the following sensitivity levels were observed: BG8+B72.3: 91%; BG8+Ber-EP4: 90%; B72.3+Ber-EP4: 93%; BG8+Ber-EP4+B72.3: 95%. The detection of malignant cells in effusions is facilitated by the use of immunocytochemistry using a wide panel of antibodies. BerEP4 and B72.3 appear to be the best markers when both sensitivity and specificity are considered, followed by BG8, while CEA and CA-125 have a limited role in the detection of metastases from gynaecological tumours owing to the low sensitivity of the former and the low specificity of the latter. Analysis of all staining results should be based on a thorough morphological examination.

Adolescent↗
PubMed1999

Psychiatric and social outcome following liver transplantation for alcoholic liver disease: a controlled study.

Psychiatric outcome, quality of life, and alcohol consumption were compared between patients transplanted for alcoholic liver disease and those transplanted for other chronic liver diseases. Instruments used included the Clinical Interview Schedule, the 28-item General Health Questionnaire, the Hospital Anxiety and Depression Scale, and the Nottingham Health Profile. There was no difference between the two groups with regard to median scores or "caseness" on these instruments, except for physical mobility on the Nottingham Health Profile, where the alcoholic group was more likely to experience difficulties (p = 0.03). The majority of those transplanted for alcoholic liver disease remained abstinent, although 7 of the 31 in the alcoholic group (23%) were drinking above recommended safe limits. Psychosocial outcome is similar for individuals transplanted for alcoholic liver disease and those transplanted for other chronic liver diseases. Patients should not be excluded from transplantation on grounds of their drinking history.

Adult↗
PubMed1999

High levels of MMP-2, MMP-9, MT1-MMP and TIMP-2 mRNA correlate with poor survival in ovarian carcinoma.

The object of this study was to analyze the potential association between the expression of MMP-2, MMP-9, MT1-MMP and TIMP-2, and disease outcome in advanced-stage ovarian carcinomas. Sections from 70 paraffin-embedded blocks (36 primary ovarian carcinomas and 34 metastatic lesions) from 45 patients diagnosed with advanced stage ovarian carcinomas (FIGO stages III-IV) were studied using mRNA in situ hybridization (ISH) technique. Patients were divided retrospectively in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period for patients that were diagnosed with advanced-stage carcinoma was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Intense mRNA signals were detected more frequently in tumor cells of short-term survivors with use of all four probes. Comparable findings were observed in peritumoral stromal cells with ISH for MMP-2, MMP-9 and TIMP-2 mRNA. Notably, primary tumors with intense mRNA signal for TIMP-2 (No = 14) were uniformly associated with a fatal outcome. In univariate analysis of primary tumors, mRNA levels of TIMP-2 in stromal cells (P = 0.0002), as well as for MMP-9 (P = 0.012) and TIMP-2 (P = 0.02) in tumor cells, correlated with poor outcome. In univariate analysis of metastatic lesions, mRNA levels of TIMP-2 in stromal cells (P = 0.031), as well as for MMP-2 (P = 0.027) and MT1-MMP (P = 0.008) in tumor cells, correlated with poor outcome. Interestingly, the presence of MT1-MMP in stromal cells correlated with longer survival (P = 0.025). In a multivariate analysis of ISH results for primary tumors, TIMP-2 levels in stromal cells (P = 0.006) and MMP-9 levels in tumor cells (P = 0.011) retained their predictive value. We conclude that MMP-2, MMP-9, MT1-MMP and TIMP-2 are valid markers of poor survival in advanced-stage ovarian carcinoma.

Adult↗
PubMed1999

Poly-L-lysine improves gene transfer with adenovirus formulated in PLGA microspheres.

In vivo gene transfer with recombinant adenovirus vectors can be hindered by the immunogenicity of the adenovirus capsid proteins. Previous work showed that formulation of the vector with biodegradable polymers such as poly-lactic-glycolic acid (PLGA), polyethylene glycol (PEG), or lipids, may shield the virus from inhibition by neutralizing antibodies. Formulation of adenovirus in PLGA microspheres also allowed for extended release in vitro. In experiments described here, we found that the surfactant used in the formation of the primary emulsion could significantly improve the overall yield of virus released. We also tested the effects of adding poly-L-lysine to adenovirus before encapsulation with PLGA. Our results show that although PLL did not effect the yield of virus encapsulated or released from the microspheres, it significantly improved the efficiency of gene transfer after release from the polymer.

Adenoviridae↗
PubMed1999

Evaluation of lymphoid cell populations in cytology specimens using flow cytometry and polymerase chain reaction.

Differential diagnosis between lymphomas and reactive lymphoid proliferations often requires ancillary techniques and morphologic evaluation. Flow cytometry (FCM) and polymerase chain reaction (PCR) can aid the detection of monoclonal B-cell populations. In the present study, the sensitivity and specificity of these two methods in the study of cytology specimens were compared. Eighty-six cytologic specimens from 81 patients (lymph nodes, solid organs, and body cavities) were evaluated. These specimens were taken from three groups of patients: those who underwent an initial evaluation for suspected lymphoma; those who were previously diagnosed with B-cell lymphoma and were now evaluated for possible disease recurrence; and those who were diagnosed with a nonhematologic malignancy. Histologic diagnosis was available for 51 samples. All samples were tested by FCM for the detection of monoclonality using kappa:lambda ratio and for clonal immunoglobulin heavy chain (IgH) gene rearrangements using a single-round PCR after cytologic evaluation. Tissue morphology, FCM and PCR results, and clinical findings in specimens without histologic diagnosis were correlated. Histologic evaluation (N = 51) revealed 44 specimens with B-cell malignancy. Twenty of the 44 lymphoma specimens (45%) were accurately diagnosed in cytologic smears, 18 (41%) were classified as suspicious of lymphoma, and 6 (14%) were diagnosed as reactive. FCM had superior sensitivity compared with PCR (77% vs. 64%). Fifty-six percent of specimens with B-cell malignancy were FCM+/PCR+, 23% were FCM+/PCR-, 14% were FCM-/PCR+, and 7% were FCM-/PCR-. The combined use of FCM and PCR resulted in a diagnosis of B-cell lymphoma in 41 (93%) of 44 B-cell lymphoma specimens and increased the sensitivity of fine needle aspiration by 48%. Both FCM and PCR aid in the diagnosis of lymphoid lesions in cytology specimens, and both can detect monoclonal B-cell populations that may be interpreted in cytology smears as reactive, even by experienced cytologists. Although FCM had higher sensitivity than PCR test in the present study, their combined use should be considered because of a relatively large number of specimens that were detected as monoclonal only with PCR.

Biopsy, Needle↗
PubMed1999

Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens.

BACKGROUND: The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients. METHODS: In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months. RESULTS: At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis. CONCLUSIONS: HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis.

Acute Disease↗
PubMed1999

Expression of metalloproteinases endometrial stromal sarcoma: immunohistochemical study using image analysis.

AIM: To investigate the expression of matrix metalloproteinases (MMP), a group of proteolytic enzymes with a central role in extracellular matrix invasion and degradation, in stromal sarcomas. METHODS: 11 endometrial stromal sarcomas (four low grade tumours, seven high grade) were stained for MMP-2, MMP-3, and MMP-9 using immunohistochemical stains. The surgical material consisted of nine hysterectomy specimens and two pelvic recurrences. Three hysterectomy specimens, removed for leiomyomas, were studied as controls. Staining area was evaluated using image analysis. RESULTS: Age at the time of diagnosis ranged from 21 to 67 years. Four of the 11 patients (three with high grade tumours and one with a low grade tumour) died of the disease, six remained free of disease, and one was lost to follow up. Staining for MMP-2, MMP-3, and MMP-9 was more diffuse in high grade tumours than in low grade tumours and controls. Staining for MMP-3 and MMP-9 was more pronounced in high grade than in low grade tumours (p = 0.04; p = 0.05). Staining for MMP-9 was significantly greater in all stromal sarcomas than in controls (p < 0.001 for high grade tumours v controls; p < 0.01 for low grade tumours v controls). Diffuse staining for MMP-2, exceeding 90% of the tumour area, was observed in three of seven high grade tumours but in no low grade tumours. There was no apparent correlation between staining for any of the three enzymes and survival. CONCLUSIONS: Both low and high grade endometrial stromal tumours express matrix metalloproteinases. MMP-3 and MMP-9 are expressed more diffusely in high grade than in low grade tumours. In the individual case, diffuse staining for MMP-2 appears to best characterise the high grade tumours. Thus staining for MMP-2 may aid in differentiating high grade from low grade tumours, and MMP-9 in differentiating normal endometrial stroma from low and high grade endometrial stromal sarcomas. MMP expression does not appear to predict disease outcome in endometrial stromal sarcoma.

Adult↗
PubMed1999

A phenylalanine hydroxylase gene from the nematode C. elegans is expressed in the hypodermis.

We have identified an aromatic amino acid hydroxylase gene from the nematode C. elegans that likely encodes the worm phenylalanine hydroxylase (PheH). The predicted amino acid sequence is most similar to that of other PheH and TrpH proteins. Reporter gene fusions and staining with an antibody to mammalian PheH indicate the gene is expressed in hypodermal cells. A fusion protein expressed in bacteria can convert phenylalanine to tyrosine, and, to a lesser extent, tryptophan to 5-hydroxytryptophan. We hypothesize that the protein is necessary to produce additional tyrosine for protein cross-linking in the nematode cuticle.

Amino Acid Sequence↗
PubMed1999

The effect of leg strength on the incidence of lower extremity overuse injuries during military training.

This study examined the effects of strength, aerobic fitness, and activity profile on the incidence of overuse injuries, particularly stress fractures, during military training. A total of 136 military recruits were followed during 9 weeks of basic training. Maximal strength and aerobic fitness were determined by a one-repetition maximum leg press and a 2,000-m run, respectively. An activity profile was determined by the recruit's activity history. Twelve recruits (8.8%) were diagnosed with stress fractures. Recruits who were 1 SD below the population mean in both absolute (98.4 +/- 36.6 kg) and relative strength (1.72 +/- 0.61 kg/kg of body weight) had a five times greater risk for stress fracture (p < 0.05) than stronger recruits. Poor aerobic fitness did not appear to be related to any increased incidence of stress fracture. It appears that recruits with lower body strength levels, within 1 SD of the population mean, have a reduced incidence of stress fractures during military training.

Adolescent↗
PubMed1999

Macrophage infiltration and angiogenesis in cervical squamous cell carcinoma--clinicopathologic correlation.

BACKGROUND: The role of angiogenesis and inflammatory cell response in predicting disease outcome was evaluated in various malignant tumors. However, the data relating to cervical cancer remains equivocal. This study evaluates the prognostic significance of microvessel counts and peritumoral macrophage infiltrates in squamous cell carcinoma of the uterine cervix. METHODS: Seventy-five cervical squamous cell carcinomas were stained immunohistochemically by two endothelial markers- anti-CD31 and Ulex Europaeus lectin I (UEA-I), and the macrophage- specific marker anti-CD68. Microvessel and macrophage counts were performed using a grid at X200 and X400 magnification, respectively, in areas of maximal density ('hot spots'). Five fields were scanned. Microvessel counts were correlated with macrophage density, and both were correlated with patient age, tumor stage, histological grade, and survival. RESULTS: Microvessel counts were comparable for ulex lectin (mean 6.8+/-4.8/field) and CD31 (8.7+/-5.3/field), and results by both markers correlated (p<0.001). Counts by both markers correlated with tumor stage, being higher in stages Ib-II compared to stage III-IV tumors (p<0.05). No correlation with age, grade, or survival was found. Macrophage counts (mean 13.1+/-12.3 cells/field) did not correlate with any of the clinical parameters studied or with microvessel counts. CONCLUSIONS: Microvessel counts and macrophage density do not correlate with survival in cervical cancer. Neither do they appear to be inter-related. The association between elevated microvessel counts and localized disease may reflect peak angiogenic stimuli by neoplastic cells. We hypothesize that the beneficial role of macrophages in cellular immunity may be opposed by the elaboration of growth factors in the vicinity of neoplastic cells.

Adult↗