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Biomedical subjects

D Gal

Publications and source records attributed to D Gal.

At least 19 recordsLinked to original sources

Fibrin microbeads (FMB) as a 3D platform for kidney gene and cell therapy.

Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.

Cell Differentiation↗

Sonographic diagnosis of Fallopian tube carcinoma.

Primary Fallopian tube carcinoma (FTC) is one of the rarest gynecological malignancies, accounting for 0.18% to 1.6% of all malignant neoplasms of the female reproductive tract. Preoperative diagnosis of FTC has been previously reported; however, most patients with FTC undergo laparotomy with a presumed diagnosis of ovarian carcinoma. The final diagnosis of FTC is usually established at the time of surgery or on pathological examination. To our knowledge, this is the first report in the English scientific literature in which the preoperative diagnosis of FTC was established by the presence of an adnexal mass with an incomplete septation on transvaginal sonography.

Adenocarcinoma↗

Preliminary report on the northern Australian melioidosis environmental surveillance project.

An environmental surveillance programme was developed to determine whether water supplies could be a source of Burkholderia pseudomallei as noted during previous melioidosis outbreak investigations. Water supplies to communities in the three northern Australian jurisdictions (Western Australia, Northern Territory and Queensland) were sampled periodically during 2001 and 2002. Water and soil samples were collected from communities known to have had recent culture-positive melioidosis cases and nearby communities where no cases had been diagnosed. Clinical isolates of B. pseudomallei obtained from northern Australian patients during 2001 and 2002 were compared with the environmental B. pseudomallei isolates by ribotyping and pulsed-field gel electrophoresis. B. pseudomallei was isolated from 11 distinct locations, all in the Northern Territory, seven of which were associated with culture-positive melioidosis cases (>1 case at three locations). Water was implicated as a possible environmental source of melioidosis in six locations. A variety of free-living amoebae including Acanthamoeba and Hartmannella spp. that are potential hosts to B. pseudomallei were recovered from environmental specimens. Culturable B. pseudomallei was not found to be widely dispersed in the environments sampled.

Animals↗

Burkholderia pseudomallei virulence: definition, stability and association with clonality.

Clinical presentations of melioidosis, caused by Burkholderia pseudomallei are protean, but the mechanisms underlying development of the different forms of disease remain poorly understood. In murine melioidosis, the level of virulence of B. pseudomallei is important in disease pathogenesis and progression. In this study, we used B. pseudomallei-susceptible BALB/c mice to determine the virulence of a library of clinical and environmental B. pseudomallei isolates from Australia and Papua New Guinea. Among 42 non-arabinose-assimilating (ara(-)) isolates, LD(50) ranged from 10 to > 10(6) CFU. There were numerous correlations between virulence and disease presentation in patients; however, this was not a consistent observation. Virulence did not correlate with isolate origin (i.e. clinical vs environmental), since numerous ara(-) environmental isolates were highly virulent. The least virulent isolate was a soil isolate from Papua New Guinea, which was arabinose assimilating (ara(+)). Stability of B. pseudomallei virulence was investigated by in vivo passage of isolates through mice and repetitive in vitro subculture. Virulence increased following in vivo exposure in only one of eight isolates tested. In vitro subculture on ferric citrate-containing medium caused attenuation of virulence, and this correlated with changes in colony morphology. Pulsed-field gel electrophoresis and randomly amplified polymorphic DNA typing demonstrated that selected epidemiologically related isolates that had variable clinical outcomes and different in vivo virulence were clonal strains. No molecular changes were observed in isolates after in vivo or in vitro exposure despite changes in virulence. These results indicate that virulence of selected B. pseudomallei isolates is variable, being dependent on factors such as iron bioavailability. They also support the importance of other variables such as inoculum size and host risk factors in determining the clinical severity of melioidosis.

Animals↗

Local delivery of a hydrophobic heparin reduces neointimal hyperplasia after balloon injury in rat carotid but not pig coronary arteries.

BACKGROUND: Intimal hyperplasia following percutaneous interventional vascular procedures is a major cause of restenosis. Although heparin inhibits intimal hyperplasia, it has not proven clinically useful in part due to an inadequate duration of intramural drug residence. This study was designed to evaluate the efficacy of local delivery of hydrophobic heparin (PTIR-RS-1), exhibiting increased intramural binding, on neointimal hyperplasia after angioplasty injury. METHODS AND RESULTS: PTIR-RS-1 was delivered locally into rat carotid arteries at three doses: 0.1 mM (440 IU), 0.3 mM (1320 IU), or 1.0 mM (4400 IU). Animals were killed at 14 days. In the pig, the doses tested were the low dose in the rat and a high dose 1 log higher. Animals were killed 28 days later. Morphometric analysis was performed to evaluate the intima: media ratio in rats and the normalized neointimal area in pigs. In rats a significant reduction in neointimal to medial area ratio from 0.73 +/- 0.15 for control vs 0.80 +/- 0.27 for sodium heparin (P = NS) and 0.15 +/- 0.07 for the 0.1 mM PTIR-RS-1 dose (P < 0.008). In pigs, PTIR-RS-1 the high dose reduced the normalized neointimal area by 16%, a difference that was not statistically significant. CONCLUSIONS: Increased hydrophobicity of heparin reduced neointimal area following balloon overstretch injury in the rat carotid but not the pig coronary artery model. This study attests to the importance of performing studies evaluating the pharmacologic effect of local delivery of a medication in at least two animal models of restenosis.

Animals↗

Contemporary surgical management of borderline ovarian tumors: a survey of the Society of Gynecologic Oncologists.

OBJECTIVE: The objective of this study was to review the current practice patterns regarding the surgical management of borderline ovarian tumors. METHODS: A one-page survey was mailed to the members of the Society of Gynecologic Oncologists (SGO), using the directory of the Society. The survey addressed the demographics of the respondent and the recommended staging procedure for presumed early-stage disease. RESULTS: Of the 660 surveys mailed, 274 (42%) were returned. Ninety-seven percent (267/274) of respondents advocate surgical staging. Of this group, 96% (257/267) perform peritoneal washings, 97% (259/267) sample the omentum, and 92% (245/267) submit random peritoneal biopsies. Eighty-eight percent (235/267) perform lymph node sampling: paraaortic biopsies by 89% (210/235) and pelvic biopsies by 97% (228/235). Of this latter group, 91% sample the external iliac chain, 82% submit hypogastric nodal tissue, and 70% remove obturator lymph nodes. CONCLUSION: Diversity exists in the surgical management of borderline ovarian tumors among members of the SGO who responded to this survey. Efforts to ensure a consistent approach to the management of borderline ovarian tumors are warranted.

Biopsy↗

Isolation of a novel gene, TSP50, by a hypomethylated DNA fragment in human breast cancer.

A novel gene, testes-specific protease 50 (TSP50), was isolated from a human testes cDNA library by using a genomic DNA probe, BR50. BR50 was isolated by a modified representational difference analysis (RDA) technique due to its hypomethylated feature in a breast cancer biopsy. This altered DNA methylation status was also detected by BR50 in other breast and some ovarian cancer tissues. The TSP50 gene product is a homologue to several human proteases, which indicates that it may encode a protease-like protein. Northern analysis of 16 different types of normal human tissues suggests that TSP50 was highly and specifically expressed in human testes, which indicates that it might possess a unique biological function(s) in that organ. Methylation status analysis in normal human testes and other tissues showed a correlation between DNA methylation and gene expression. Most importantly, reverse transcription-PCR analysis of 18 paired breast cancer tissues found that in 28% of the cancer samples, the TSP50 gene was differentially expressed. The possibility that TSP50 may be an oncogene is presently under investigation.

Amino Acid Sequence↗

Synchronous Paget's disease of the vulva and breast.

We report the first case of synchronous Paget's disease of the vulva and breast diagnosed within a period of 7 months. This is the fourth case of mammary Paget's disease associated with either preceding or following vulvar Paget's disease documented in the literature. With consideration of increasing age of the population, and the fact that vulvar Paget's disease affects elderly women and that breast cancer is the most common malignancy of women in the United States, one can anticipate the occurrence of these two conditions to be more prevalent in the future.

Breast Neoplasms↗

Prophylactic ureteral catheterization in gynecologic surgery.

OBJECTIVES: To examine the frequency of ureteral catheter usage, its efficacy in preventing injury, and related complications, because the preoperative routine placement of ureteral catheters as a prophylactic measure to prevent ureteral injury is controversial. METHODS: All major gynecologic operations performed between January 1992 and December 1994 were identified. All gynecologic procedures that were preceded by ureteral catheter placement were also identified. A data base maintained by the Department of Quality Management allowed identification of all urinary tract complications and ureteral injuries. Four categories of surgery were analyzed: exploratory laparotomy with catheters, exploratory laparotomy without catheters, operative laparoscopy with catheters, and operative laparoscopy without catheters. The medical records of all patients with urinary tract complications were reviewed. RESULTS: Bilateral prophylactic ureteral catheterization was performed in 469 (15.3%) of 3071 patients. A ureteral injury occurred in 4 (0.13%) of 3071 patients. All four ureteral injuries (0.17%) occurred among 2338 patients who underwent exploratory laparotomy. None of the 733 patients who underwent operative laparoscopy suffered ureteral injury. The incidence of ureteral injury in patients who had ureteral catheters placed before exploratory laparotomy was 2 (0.62%) of 322. Two (0.10%) of 2016 patients who did not have prophylactic ureteral catheters suffered a ureteral injury. There was no statistically significant difference in the incidence of ureteral injury between patients who did and patients who did not undergo ureteral catheterization (P=0.094). CONCLUSIONS: The use of prophylactic ureteral catheters did not affect the rate of ureteral injury in our patients. The very low incidence of ureteral injury among our patients is attributed mainly to meticulous surgical technique.

Female↗

Changes in the shape and orientation of periodontal ligament fibroblasts in the continuously erupting rat incisor following removal of the occlusal load.

One of the main theories which attempts to explain the phenomenon of tooth eruption suggests that periodontal ligament (PDL) fibroblasts move actively and pull the tooth with them out of its socket. To find further support for this theory, we determined the changes in the shape and orientation of PDL fibroblasts induced by a transition from impeded to unimpeded eruption. We measured nuclear area, elongation (length-to-width ratio), and orientation (angulation in relation to the eruption axis) of PDL fibroblasts in impeded (functionally loaded) and unimpeded (hypoloaded) rat incisors. The mean cross-sectional nuclear area did not differ between fibroblasts in the two groups. In contrast, unimpeded eruption resulted in a marked increase in the mean nuclear elongation (from about 2 to 2.56) and a significant increase in the mean nuclear orientation (from 25.6 to 14.0 degrees). Bivariate analysis suggested that these changes occurred in the same cells. Analysis of nuclear elongation and orientation at various distances from the cementum toward the alveolar bone revealed a profile of both parameters, such that cells located 20 to 80 microns away from the cemental surface were more elongated and more frequently oriented toward the eruption axis, while cells at 0 to 20 and 80 to 100 microns were more round/oval and had a greater angulation with the eruption axis. These findings, together with other observations of changes in cell number, number of microtubules, and migration velocity which occur on the shift to unimpeded eruption, support the theory of active movement of PDL fibroblasts as an important component of tooth eruption.

Animals↗

Pelvic control following external beam radiation for surgical stage I endometrial adenocarcinoma.

PURPOSE: To determine if postoperative external pelvic radiation (EBRT), without vaginal brachytherapy, is sufficient to prevent vaginal cuff and pelvic recurrences in patients with surgical Stage I endometrial adenocarcinoma (ACA). METHODS AND MATERIALS: The records of 122 patients with surgical Stage I endometrial cancer were reviewed. There were 87 patients with ACA who received EBRT alone and are the subject of this study. Their radiation records were reviewed. All patients underwent exploration, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH BSO), and pelvic and paraaortic lymph node sampling. They were staged according to the FIGO 1988 surgical staging system recommendations. Postoperatively, pelvic EBRT was administered by megavoltage equipment using four fields, to a total dose of 45 to 50.4 Gy. Actuarial survival and disease free survival were calculated according to Kaplan-Meier Method. RESULTS: Twenty-seven patients with Stage IA Grade 1 or 2 ACA with less than one-third myometrial invasion, who did not receive EBRT, and eight patients with histology other than adenocarcinoma (i.e., serous papillary, mucinous, etc.) were not included in the study. For the remaining 87 patients who are in the study group, the median follow-up was 52 months (range: 12-82 months). The 5-year overall survival for these 87 patients was 92%, with a disease-free survival of 83%. There were no tumor recurrences in the upper vagina or in the pelvis. Two patients developed small bowel obstruction (no surgery required), and one patient developed chronic enteritis. CONCLUSION: Adjuvant external pelvic radiation, without vaginal brachytherapy, prevents pelvic and vaginal cuff recurrences in surgical Stage I endometrial ACA.

Adenocarcinoma↗

Primary adenoid cystic carcinoma of Skene's glands.

A unique case of a 50-year-old woman is reported who presented with a suburethral mass in the anterior vaginal wall. The resected tumor was an adenoid cystic carcinoma arising from Skene's glands. Tumor was not involving Bartholin's glands. In addition to the typical glands and areas with cysts containing periodic acid-Schiff positive intraluminal material, less well-differentiated areas with neoplastic cells growing in a trabecular or solid pattern were also seen. Prominent perineural invasion was noted throughout the tumor. Immunostaining revealed positive reactions for cytokeratins, carcinoembryonic antigen, and focally for S-100 protein. Ultrastructural studies showed epithelial cells with well-formed basal lamina and prominent microvilli. This case illustrates an uncommon site, the Skene's glands for adenoid cystic carcinoma in the female genitourinary tract.

Carcinoma, Adenoid Cystic↗

Pharmacokinetic evaluation of zeniplatin in humans.

Zeniplatin, a more water-soluble organoplatinum than cisplatin, was evaluated for clinical pharmacology in the context of a phase II trial in previously treated patients with ovarian carcinoma. A total of 12 patients were given zeniplatin at 120 mg/m2 by rapid intravenous infusion over 90 min, with both blood and urine being sampled. All platinum moieties were analyzed in whole blood, plasma, plasma ultrafiltrate, and urine by atomic absorption, and free zeniplatin was analyzed in plasma ultrafiltrate by specific high-performance liquid chromatography (HPLC). In a comparison of the platinum-time concentration curve, AUC (area under the curve) values indicated that approximately 90% of platinum moieties were bound to circulating plasma proteins. There was no evidence of drug accumulation after repetitive dosing. The terminal half-life (t1/2) of this drug in plasma ultrafiltrate (3.7-7.2 h.) as measured by HPLC was slightly longer than that of carboplatin, whereas total platinum moieties in plasma displayed a long t1/2 (124-154 h). Approximately 60% of platinum moieties could be recovered in the urine within 24 h. These findings suggest that zeniplatin has a pharmacokinetic profile similar to that of carboplatin.

Adult↗

Comparative study of laparoscopy vs. laparotomy for adnexal surgery: efficacy, safety, and cyst rupture.

Operative laparoscopy is becoming routine in gynecologic surgery. This study was designed to compare the safety and efficacy of laparoscopy and laparotomy for ovarian cystectomy and adnexectomy. The medical records of 32 patients who underwent operative laparoscopy for adnexal masses (group L) were reviewed and compared with those of 32 patients who underwent surgical laparotomy (group S) for similar indications. All patients sustained either an ovarian cystectomy or adnexectomy. The group were matched for age, weight, and history of previous laparotomy. Median operating time for group L was 90 min and for group S was 85 min. Blood loss was significantly less in group L (33.4 +/- 22 mL) than in group S (84.6 +/- 22.2 mL), p < 0.0001. There were two intraoperative complications in group L and one in group S. Significantly less patients in group L had postoperative fevers (16%) as compared with those in group S (69%), p < 0.0001. There was a higher incidence of cyst rupture when cystectomy was performed in patients from group L (7 of 21) as compared with patients from group S (2 of 17). No such difference in cyst rupture was noted when an adnexectomy was affected in group L (1 of 11) and group S (1 of 15). Patients in group L remained in the hospital a shorter time period, 1.5 +/- 0.8 days, than patients in group S, 4.7 +/- 0.9 days, p < 0.0001. Patients in group L required a shorter postoperative recovery time before resuming normal activities, 9.1 +/- 6.6 days, than patients in group L, 27.5 +/- 9.2 days, p < 0.0001. Similarly, patients in group L required less time to become pain free, 10.1 +/- 7.4 days, than patients in group L, 17.7 +/- 6.1 days, p < 0.0005. This study demonstrates a statistically significant decrease in postoperative morbidity and faster recovery in patients undergoing laparoscopy for adnexal surgery as compared with patients undergoing laparotomy for the same procedure. When cystectomy is performed via the laparoscope, there is a higher incidence of cyst rupture than with laparotomy.

Adnexa Uteri↗