Search PubMed⌕ Search

Biomedical subjects

C V Smith

Publications and source records attributed to C V Smith.

At least 19 recordsLinked to original sources
PubMed2004

External beam radiation therapy after radical prostatectomy: efficacy and impact on urinary continence.

INTRODUCTION AND OBJECTIVES: The efficacy of adjuvant and salvage external beam radiation (AXRT+SXRT) for prostate cancer after radical prostatectomy (RP) has been debated because of the inability to rule out systemic occult metastasis, uncertainty that radiation eradicates residual local disease and the potential of exacerbating impotency and incontinence. To characterize the effectiveness and treatment morbidity a retrospective review was performed. METHODS: In all, 38 patients received AXRT and 91 received SXRT. The SXRT group was stratified by PSA level, age, race, pathologic stage, margin status, worst Gleason sum, radiation dose and pelvic field. Complications evaluated were impotence and incontinence. Median follow-up was 60.2 months. RESULTS: The 5-y disease-free survival (DFS) rate was 61.3% for AXRT and 36.3% for SXRT. Multivariate analysis of the SXRT cohort showed Gleason score, pathologic stage and pre-XRT PSA to be predictors of disease recurrence. After XRT 26% had worsened continence. CONCLUSIONS: Patients who recur after RP whose pathologic stage is pT2 or pT3c, Gleason score of 8 or higher or pre-XRT PSA is >2.0 ng/dl may have microscopic metastatic disease and a decreased chance of cure with SXRT alone. Continence was further impaired after XRT.

Aged↗
PubMed2003

The TB structural genomics consortium: a resource for Mycobacterium tuberculosis biology.

The TB Structural Genomics Consortium is an organization devoted to encouraging, coordinating, and facilitating the determination and analysis of structures of proteins from Mycobacterium tuberculosis. The Consortium members hope to work together with other M. tuberculosis researchers to identify M. tuberculosis proteins for which structural information could provide important biological information, to analyze and interpret structures of M. tuberculosis proteins, and to work collaboratively to test ideas about M. tuberculosis protein function that are suggested by structure or related to structural information. This review describes the TB Structural Genomics Consortium and some of the proteins for which the Consortium is in the progress of determining three-dimensional structures.

Amino Acid Sequence↗
PubMed2001

Display of complete life cycle of human papillomavirus type 16 in cultured placental trophoblasts.

Human papillomavirus (HPV) infection is threefold more prevalent in spontaneous abortion specimens compared to elective abortions preferentially targeting the placental trophoblasts in these specimens. Here by using infectious ceplar and Southern blot analysis, we demonstrate that the transfected HPV-16 genome de novo replicates in 3A trophoblasts in culture. Peak DNA replication occurred 9-24 days posttransfection, showing classic DNA forms I, II, and III and an 8-kb monomer band upon DpnI/BamHI digestion. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA expression revealed that E6 and E2 were significantly expressed by day 9, coinciding with HPV-16 DNA replication. However, significant L1 expression was delayed until day 18. L1 protein expression on day 18, but not day 9, was also confirmed by Western blot analysis. The production of HPV-16 virions was demonstrated by three techniques: the appearance of HPV-16 infectious units coinciding with L1 expression, the neutralization of these infectious units with known neutralizing anti-HPV-16 antibodies, and the appearance of spliced E1-E4 and E6-E7 transcripts (RT-PCR) in normal keratinocyte rafts infected with these trophoblast-produced HPV-16 infectious units. These data suggest that HPV-16 is carrying out its complete life cycle in trophoblasts. Previously, HPVs were known to productively replicate only in differentiating keratinocytes of skin. These findings expand HPV biology, support the hypothesis of a possible link between HPV and some spontaneous abortions, and present a new technology for studying HPV.

Cells, Cultured↗
PubMed2001

Mitochondrial thiol status in the liver is altered by exposure to hyperoxia.

Patients with poorly functioning lungs often require treatment with high concentrations of supplemental oxygen, which, although often necessary to sustain life, can cause lung injury. The mechanisms responsible for hyperoxic lung injury have been investigated intensely and most probably involve oxidant stress responses, but the details are not well understood. In the present studies, we exposed adult male C57/Bl6 mice to >95% O2 for up to 72 h and obtained lung and liver samples for assessment of lung injury, measurements of tissue concentrations of coenzyme A (CoASH) and the corresponding mixed disulfide with glutathione (CoASSG), as possible biomarkers of intramitochondrial thiol redox status. Subcellular fractions were prepared from both tissues for determination of glutathione reductase (GR) activities. Lung injury in the hyperoxic mice was demonstrated by increases in lung weight to body weight ratios at 48 h and by increases in bronchoalveolar lavage protein concentrations at 72 h. Lung CoASH concentrations declined in the hyperoxic mice, but CoASSG concentrations were not increased nor were CoASH/CoASSG ratios decreased, as would be expected for an oxidant shift in mitochondrial thiol-disulfide status. Interestingly, CoASSG concentrations increased (from 6.72+/-0.54 to 14.10+/-1.10 nmol/g of liver in air-breathing controls and 72 h of hyperoxia, respectively, P<0.05), and CoASH/CoASSG ratios decreased in the livers of mice exposed to hyperoxia. Some apparent effects of duration of hyperoxia on GR activities in lung or liver cytosolic, mitochondrial, or nuclear fractions were observed, but the changes were not consistent or progressive. Yields of isolated hepatic nuclear protein were decreased in the hyperoxic mice within 24 h of exposure, and by 72 h of hyperoxia, protein recoveries in purified nuclear fractions had declined from 41.8 to 14.8 mg of protein/g animal body weight. Concentrations of 10-formyltetrahydrofolate dehydrogenase were diminished in hepatic mitochondria of hyperoxic mice. A second protein in hepatic mitochondria of approximately 25 kDa showed apparent decreases in thiol content, as determined by fluorescence intensities of monobromobimane derivatives separated by SDS-PAGE. The mechanisms responsible for the observed effects and the possible implications for the adverse effects of hyperoxic therapies are not known and need to be investigated.

Animals↗
PubMed2001

Clara cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects prematurely born infants and appears to evolve in part from early inflammatory responses in the lung. The inflammatory responses have been associated with protein and lipid oxidation in tracheal aspirate fluids. The present study was designed to test the hypothesis that in the first week of life specific oxidations and/ or altered expressions of proteins would be observed in tracheal aspirate fluids in infants who would subsequently develop BPD. We obtained tracheal aspirate fluids on Days of life 1, 3, and 6 from infants born at < or = 29 wk gestation, incubated the fluids with 2,4-dinitrophenylhyrazine (DNPH), separated the proteins electrophoretically, and assessed DNPH reactivity by immunonblots. DNPH reactivity of a protein that was identified as Clara cell secretory protein (CCSP) was observed more consistently in tracheal aspirate fluids from infants who later developed BPD than from infants who did not develop BPD. Tracheal aspirate fluid levels of immunoreactive CCSP were also lower on Day of life 1 in infants who developed BPD than in those who did not develop BPD. Increased CCSP oxidation and decreased immunoreactive CCSP expression in infants who subsequently developed BPD suggest that Clara cell function and CCSP expression may be critical for normal bronchoalveolar fluid homeostasis and that maintaining CCSP expression and function may be useful goals for targeted therapies for inhibition of the development of BPD.

Analysis of Variance↗
PubMed2001

Characterization of the metabolic demands of simulated shipboard Royal Navy fire-fighting tasks.

The purpose of this study was to quantify the metabolic demand of simulated shipboard fire-fighting procedures currently practised by men and women in the Royal Navy (RN) and to identify a minimum level of cardiovascular fitness commensurate with satisfactory performance. Thirty-four males (M) and 15 females (F) volunteered as subjects for this study (n=49). Maximal oxygen uptake (VO2max) and heart rate (fcmax) of each subject was assessed during a standardized treadmill test. During the main trials, volunteers were randomly assigned to complete several 4-min simulated shipboard fire-fighting tasks (boundary cooling (BC), drum carry (DC), extinguisher carry (EC), hose run (HR), ladder climb (LC)), at a work rate that was endorsed as a minimum acceptable standard. Heart rate (fc) and oxygen uptake (VO2) were recorded at 10-s intervals during rest, exercise and recovery. Participants completed all tasks within an allocated time with the exception of the DC task, where 11 subjects (all females) failed to maintain the endorsed work rate. The DC task elicited the highest (p<0.01) group mean peak metabolic demand (PMD) in males (43 ml min(-1) kg(-1)) and females (42 ml min(-1) kg (-1)) who were able to maintain the endorsed work rate. The BC task elicited the lowest PMD (23 ml min(-1) kg(-1)), whilst the remaining three tasks elicited a remarkably similar PMD of 38-39 ml min(-1) kg(-1). The human endurance limit while wearing a self-contained breathing apparatus (SCBA) dictates that RN personnel are only able to fire-fight for 20-30 min, while wearing a full fire-fighting ensemble (FFE) and performing a combination of the BC, HR and LC tasks, which have a group mean metabolic demand of 32.8 ml min(-1) kg(-1). Given that in healthy subjects fire-fighting can be sustained at a maximum work intensity of 80% VO2max when wearing SCBA for this duration, it is recommended that all RN personnel achieve a VO2max of 41 ml min(-1) kg(-1) as an absolute minimum standard. Subjects with a higher VO2max than the above quoted minimum are able to complete the combination of tasks listed with greater metabolic efficiency and less fatigue.

Energy Metabolism↗
PubMed2001

Ocular damage due to chlorhexidine versus eyeshield thermal injury.

BACKGROUND: Ocular damage may occur from a number of mechanisms during laser use. OBJECTIVE: To review issues relevant to ocular protection during laser resurfacing. METHODS: The authors were consulted to evaluate the thermal energy transferred from the outer to the inner (ie, corneal contact) surface of stainless steel eyeshields following direct exposure to the carbon dioxide (CO2) resurfacing laser beam. Measurements were obtained using thermocouples (attached to the inner surface of the eyeshields) and analyzed with a computer-based acquisition system. RESULTS: A maximum eyeshield temperature increase of 13 degrees C above the ambient temperature was noted following one pass with a CO2 resurfacing laser (Sharplan continuous CO2 laser with Clinicon SureScan scanner, 15 W, 950 microsec pulse duration, square spot of 9 mm). CONCLUSION: The eyeshields analyzed in this study minimized thermal transfer following a single direct hit with a CO2 resurfacing laser. An understanding of the potential mechanisms of ocular injury is essential in preventing its occurrence.

Anti-Infective Agents, Local↗
PubMed2001

Increased islet viability by addition of beraprost sodium to collagenase solution.

The digestion of pancreatic tissue with collagenase is an essential part of the islet isolation procedure. However, the process exposes islets to various types of harmful factors, including collagenase contaminants, enzymes released from the acinar cells, warm ischemia, and mechanical agitation. Nitrogen oxide production and cytokine release may also contribute to islet cell damage. Protection of islets from such damage would improve the islet yield, survival, and function. Beraprost sodium (BPS) is a prostaglandin I2 analogue, is stable in aqueous solution, and has a cytoprotective effect on various types of cells. BPS has been shown to improve the yield and function of cryopreserved and/or cultured islets. These findings prompted us to examine its cytoprotective effect on islets during the islet isolation process. Canine islets were isolated by means of a two-step digestion method and purified on Euro-Ficoll density gradient solutions (the procedure used for human islets). BPS at a concentration of 100 nM was added to the collagenase solution. After purification, the islet yield was 434,561 +/- 35.691 islet number expressed as 150 microm equivalent size (IEQ)/pancreas or 8,799 +/- 345 IEQ/g of pancreas in the BPS group and 349,987 +/- 52,887 IEQ/pancreas or 7,998 +/-1610 IEQ/g of pancreas in the control group (n = 8, each). The percent viability was 88.5 +/- 0.7% in the BPS group and 82.0 +/-0.9% in the control group (P < 0.01). Therefore, the recovery of viable islets (calculated by islet number x % viability) was 384,586 +/- 46,804 IEQ/pancreas (7,743 IEQ/g) in the BPS group and 286,989 +/- 43,367 IEQ/pancreas (6,558 IEQ/g) in the control group (P < 0.02). After culture, significantly higher numbers of islets were also recovered in the BPS group than in the control group. The islet insulin content was significantly higher in the BPS group than controls (237.8 +/- 38.5 versus 92.3 +/- 25.6 microU/IEQ; P < 0.02), although islets of both groups responded with high stimulation indices (>6). These results indicate that the addition of BPS to the collagenase solution increases the recovery of viable islets, and improves beta cell function.

Animals↗
PubMed2001

Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer.

OBJECTIVES: To assess expression of the immunosuppressive cytokines IL-10 and TGF-beta in the ascitic fluid and plasma of advanced ovarian cancer patients. DESIGN: A prospective study. SETTING: The Department of Obstetrics and Gynaecology at the University of Arkansas for Medical Sciences. POPULATION: Twenty-eight women diagnosed with advanced ovarian cancer and ten normal female controls. METHODS: Plasma and ascitic samples were collected at the time of surgery and analysed for the presence of IL-10 and TGF-beta using a sensitive enzyme-linked immunosorbent assay. RESULTS: Elevated levels of IL-10 were detected in the plasma [mean (SD) = 12 (5) pg/mL; range 8 to 23 pg/mL] and in the peritoneal fluid [mean (SD) = 165 (137) pg/mL; range 50 to 556 pg/mL] of ovarian cancer patients, while no detectable IL-10 was found in any of the normal control plasma samples tested. Similarly, plasma levels of TGF-beta in ovarian cancer patients were significantly higher [mean (SD) = 1,506 (246) pg/mL; range 1,020 to 2,070 pg/mL] compared with controls [mean (SD) = 937 (187) pg/mL; range 770 to 1,140 pg/mL](P < 0.001). Surprisingly, however, although elevated TGF-beta levels were also detected in the peritoneal fluid of all ovarian cancer patients [mean (SD) = 407 (158) pg/mL; range 140 to 770 pg/mL], these levels were significantly lower than those seen in matched plasma samples (P < 0.001). CONCLUSIONS: Local and systemic secretion of immunosuppressive cytokines may play an important role in the impaired anti-tumour immune function commonly observed in advanced ovarian cancer. However, the observation that plasma levels of TGF-beta are significantly higher than those detected in the ascitic fluid raises the possibility that cells other than tumour cells are responsible for TGF-beta release in the bloodstream of these patients.

Adult↗
PubMed2001

Rationale for antioxidant therapy in premature infants to prevent bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in premature infants that can cause severe complications. BPD's pathogenesis is multifactorial but oxidative processes during the first week of life are thought to play a key role in the development of the disease. Prevention of this oxidation through antioxidant therapy is therefore of interest. Unfortunately, this therapy has not proven effective, most likely owing to the nonspecific strategy used. This review focuses on the challenges facing researchers and clinicians in improving the antioxidant status of premature infants in order to prevent or lessen the severity of BPD. This review will focus on the particular oxidations that may lead to BPD and the specific therapies that can be used to counter these processes.

Antioxidants↗
PubMed2001

Phenotypic and functional analysis of tumor-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and peripheral blood lymphocytes in patients with advanced ovarian cancer.

To investigate and compare the phenotype and function of lymphocytes collected from patients harboring advanced ovarian cancer, leukocytes from peripheral blood (n = 18), ascitic fluid (n = 13) and tumor tissues (n = 13) were evaluated for the relative proportions of lymphocyte subsets, including CD3+, CD4+, CD8+, CD19+, CD56 and the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells. The ability to synthesize type 1 cytokines (IFN-gamma and IL-2) and a type 2 cytokine (IL-4) was assessed by flow cytometry. In all patients, T cells (CD3+) were the major leukocyte population detected in each tissue, with CD4+ T cells being dominant in peripheral blood lymphocytes (PBL) and tumor-associated lymphocytes (TAL) but not in tumor-infiltrating lymphocytes (TIL) (CD4:CD8 ratios: 3.0 vs. 2.0 vs. 1.0, respectively). CD19+ lymphocytes (B cells) and CD56+ lymphocytes (NK cells) were significantly higher in PBL compared to TAL and TIL (p < 0.05). TAL and TIL had a higher proportion of T cells expressing the late activation marker HLA-DR compared to PBL. In contrast, no significant differences were detected in PBL, TAL and TIL in the expression of the early activation marker CD25. Type 1 cytokines were the dominant type produced by in vitro stimulated T cells for each population, with a greater proportion of IFN-gamma+ T cells in TAL and TIL compared to PBL (p < 0.01), and a higher proportion of IL-2+ T cells in PBL compared with TAL and TIL (p < 0.05). Low percentages of IL-4+ T cells (i.e. Th2) were detected in each tissue. Taken together, these data demonstrate the recruitment and accumulation of high concentrations of antigen-experienced T lymphocytes in TAL and TIL compared to PBL. However, low surface expression of IL-2 receptor (i.e. CD25), as well as depressed intracellular IL-2 production in chronically stimulated TAL and TIL suggests that the impaired antitumor function commonly detected in these lymphocyte populations may be secondary to an acquired dysregulation of the IL-2 pathway.

Adult↗
PubMed2001

Prolongation of islet allograft survival in mice by combined treatment with pravastatin and low-dose cyclosporine.

Pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is known to have suppressive effects on immune and inflammatory cells. We have previously shown in mice and dogs that this agent prevents primary nonfunction of islet iso- and autografts by reducing inflammation at the graft site. The present study was designed to further investigate whether pravastatin has a synergistic effect with cyclosporine (Cs) to prolong islet allograft survival in mice. Unpurified 3000 BALB/c newborn islets were transplanted under the renal capsule of a streptozotocin-diabetic C57BL/6 mouse. Pravastatin and Cs were administered for 10 days starting on the day of grafting (day 0). Five groups were set up based on the treatment protocol: group 1, treatment with 40 mg/kg pravastatin; group 2, 30 mg/kg Cs; group 3, 50 mg/kg Cs; group 4, 40 mg/kg pravastatin and 30 mg/kg Cs; group 5, vehicle alone. Graft survival was indicated by blood glucose levels sustained at <200 mg/dl, and graft rejection by >250 mg/dl for 2 consecutive days. Hyperglycemia persisted in six of the eight (75%) mice and grafts were rejected in 3.6 +/- 0.5 days (mean +/- SD) in group 5. In group 1, grafts were also rejected in 3.8 +/- 0.8 days, but blood glucose was transiently <200 mg/dl in three of the five mice. Despite Cs, grafts were rejected between 7 and 15 days (10.3 +/- 2.4 days) in group 2. Among six mice in group 3, one maintained euglycemia for >60 days, the other rejected the graft on day 15, and the remaining four died with functioning grafts between 9 and 13 days due to Cs toxicity. A combination of a low dose of Cs and pravastatin (group 4) prolonged graft survival for >19 days in five of the eight mice, and for 7-13 days in the remaining three mice. Histological examination of the grafts in this group showed significantly reduced local inflammation. Results indicate a synergistic effect of pravastatin and Cs on prevention of islet allograft rejection.

Animals↗
PubMed2001

Selective oxidation in vitro by myeloperoxidase of the N-terminal amine in apolipoprotein B-100.

In contrast to the multiple low abundance 2,4-dinitrophenylhydrazine-reactive tryptic peptides formed by oxidation of LDL with reagent HOCl in vitro, myeloperoxidase-catalyzed oxidation produces a dominant product in considerably greater yield and selectivity. This modified peptide had a single amino-terminal sequence corresponding to amino acids 53-66 of apolipoprotein B-100 (apoB-100), but its mass spectra indicated a significantly higher mass than could be reconciled with simple modifications of this peptide. Subsequent studies indicate that this product appears to result from N-chlorination of the N-terminal amino group of apoB-100 and dehydrohalogenation to the corresponding imine, which may form the hydrazone derivative directly, or after hydrolysis to the ketone. The methionine residue is oxidized to the corresponding sulfoxide, and the primary sequence peptide (residues 1-14 of apoB-100) is linked by the intramolecular disulfide bond between C-12 and C-61 to the peptide composed of residues 53-66, as we have observed previously (Yang, C-Y., T. W. Kim, S. A. Weng, B. Lee, M. Yang, and A. M. Gotto, Jr. 1990. Proc. Natl. Acad. Sci. USA. 87: 5523-5527) in unmodified LDL. The selective oxidation by myeloperoxidase of the N-terminal amine suggests strong steric effects in the approach of substrate to the enzyme catalytic site, an effect that may apply to other macromolecules and to cell surface molecules.

2,4-Dinitrophenol↗
PubMed2000

Dexamethasone enhances P-selectin mRNA expression in hyperoxic rat lungs.

OBJECTIVE AND DESIGN: To test the hypothesis that glucocorticoid administration would diminish the lung expression of P-selectin mRNA in hyperoxia-exposed rats. ANIMALS: Adult male Sprague-Dawley rats were divided into 6 separate groups containing 10 to 13 animals per group. TREATMENT: Rats were dosed with 1 mg/kg of dexamethasone or vehicle only, ip. Immediately after dosing, animals were placed in > 95 % oxygen. Some animals were maintained in room air and are presented as 0 h of exposure to hyperoxia. Another group of animals was dosed with 10 mg/kg lipopolysaccharide (LPS) ip immediately after dosing with either dexamethasone or vehicle as above. METHODS: At 24 or 48 h, lung samples were obtained, and lung weight to body weight ratios calculated. In the LPS studies, samples were obtained 4 h after LPS dosing. In a subset of animals, lung sections were hybridized for P-selectin mRNA. All data except for hybridizations were analyzed with three-way ANOVA, with subsequent post-hoc testing. P-selectin hybridizations were quantified by counting the number of positive vessels per high-powered field, and subsequently analyzed by unpaired Student's t-test. Immunohistochemical analyses for P-selectin expression were also performed to determine whether changes in P-selectin mRNA were associated with differences in protein expression. All data are expressed as means +/- SEM. RESULTS: Rats dosed with dexamethasone had higher lung/body weight ratios after 24 and 48 h of exposure to hyperoxia than did similarly exposed rats dosed only with vehicle (at 48 h, 0.87 +/- 0.04 versus 0.65 +/- 0.06, respectively, P < 0.05). The higher ratios in hyperoxic animals dosed with dexamethasone were associated with much higher levels of lung expression for P-selectin mRNA than was observed in similarly exposed rats dosed with vehicle alone (at 48 h, 3.93 +/- 1.02, versus 0.20 +/- 0.06, respectively, P < 0.01). In contrast dexamethasone dosing lead to lower lung P-selectin mRNA expression in animals exposed to LPS (1.23 +/- 1.08 in dexamethasone dosed animals versus 6.80 +/- 0.92 in vehicle only dosed animals). Consistent with the mRNA data, P-selectin immunoreactivity increased as a function of hyperoxia-exposure time in animals dosed with dexamethasone, while immunoreactivity decreased as a function of hyperoxia-exposure time in animals dosed with vehicle only. CONCLUSIONS: Increased P-selectin mRNA combined with increased P-selectin protein expression in animals exposed to hyperoxia and dosed with dexamethasone suggests that enhanced expression of P-selectin may contribute to the greater lung injury and inflammation caused by hyperoxia in rats treated with dexamethasone.

Animals↗
PubMed2000

Current progress and perspectives in immunoisolated islet transplantation.

This review summarizes the recent results of immunoioslated islet allo- and xenotransplants, especially in large animal species, and presents certain issues that would be important for the advancement of this technology toward clinical application. To date, the best results have been obtained with alginate microcapsules in both allo- and xenogeneic (porcine) islet transplantation in the spontaneously diabetic dogs and monkeys. Reversal of diabetes was also achieved in mice with cryopreserved, microencapsulated rat islets. However, results with these microcapsules have been highly variable and inconsistent from one laboratory to another. The causes of these discrepancies are multiple, but not totally understood. Immunoisolation devices have been investigated as an alternate approach to house a large number of islets in a space constructed by membranes of a defined pore size. Vascularized bioartificial devices were among the few cases that obtained long-term allo- and xenogeneic islet survival in totally pancreatectomized dogs. Thrombosis and associated problems were the major cause of failure with these devices. Diffusion chambers that have no vascular connection have been tested successfully in rodents, but no report has been available in large animal species. We have learned many important lessons and made considerable progress in islet immunoisolation. However, immunoisolated islet transplants have been only minimally successful in large animal models, and such technologies must be improved to achieve consistent success in large animal models prior to clinical trials. This will requires strict quality control of the islets, the membrane material, and the device construction. The membrane pore size that allows the permeation of molecules necessary for islet survival and function also permits the entry of cytokines, oxygen-radicals, and other small-size inflammatory products. Thus, the key to success appears to be to minimize inflammatory reactions generated by immuneisolation devices/capsules.

Alginates↗
PubMed2000

Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database.

PURPOSE: Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS: We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS: There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Adenocarcinoma↗