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Biomedical subjects

I Gal

Publications and source records attributed to I Gal.

At least 19 recordsLinked to original sources
PubMed2006

ATM haplotypes and breast cancer risk in Jewish high-risk women.

While genetic factors clearly play a role in conferring breast cancer risk, the contribution of ATM gene mutations to breast cancer is still unsettled. To shed light on this issue, ATM haplotypes were constructed using eight SNPs spanning the ATM gene region (142 kb) in ethnically diverse non-Ashkenazi Jewish controls (n=118) and high-risk (n=142) women. Of the 28 haplotypes noted, four were encountered in frequencies of 5% or more and accounted for 85% of all haplotypes. Subsequently, ATM haplotyping of high-risk, non-Ashkenazi Jews was performed on 66 women with breast cancer and 76 asymptomatic. One SNP (rs228589) was significantly more prevalent among breast cancer cases compared with controls (P=4 x 10(-9)), and one discriminative ATM haplotype was significantly more prevalent among breast cancer cases (33.3%) compared with controls (3.8%), (P< or =10(-10)). There was no significant difference in the SNP and haplotype distribution between asymptomatic high-risk and symptomatic women as a function of disease status. We conclude that a specific ATM SNP and a specific haplotype are associated with increased breast cancer risk in high-risk non-Ashkenazi Jews.

Adult↗
PubMed2004

[Results of laparoscopic repair of abdominal wall hernias using an ePTFE-polypropylene composite mesh].

BACKGROUND: The standard technique for laparoscopic ventral hernioplasty (peritoneal onlay) reduces the recurrence rate and the rate of other complications, in particular the risk of infections. However, the procedure requires a special mesh to mitigate the risk of visceral adhesions. For this purpose an ePTFE mesh is generally used. There are limited reported clinical data regarding the long-term results and benefits of other biomaterials. STUDY DESIGN: Bard Composix mesh was used for laparoscopic ventral hernia repair. This biomaterial combines two different clinically proven materials--polypropylene with a thin layer of ePTFE--to maximize ingrowth of surrounding tissue, while mitigating the risk of visceral adhesions. Demographic, operative and postoperative data were collected and analyzed. Follow-up clinical evaluations were conducted 6-10 days, 4 weeks, and every 6 (th) month after surgery in all patients. RESULTS: Fifteen patients were involved in the study. The mean operating time was 101.2 min (64-190 min). There were no intraoperative complications or conversion to open procedure. Postoperative complications were 1 seroma, 4 cases of prolonged ileus, one tacks-site pain requiring second-look laparoscopy. Hospital discharge occurred on average 6 days (3-10 days) after surgery. The mean follow-up was 12.4 months (range 5-29 months). No late complications or hernia recurrence were observed. CONCLUSIONS: Laparoscopic prosthetic ventral hernioplasty using the composite polypropylene/ePTFE mesh offers short hospital stay and acceptable complications for primary and recurrent ventral hernias. Disadvantage of the composite mesh is the difficulty to roll this product into a sufficiently small size to permit its easy introduction into the abdominal cavity.

Adult↗
PubMed2000

Natural history of individuals with asymptomatic disc abnormalities in magnetic resonance imaging: predictors of low back pain-related medical consultation and work incapacity.

STUDY DESIGN: Prospective study on individuals with asymptomatic lumbar disc abnormalities detected in magnetic resonance imaging. OBJECTIVES: To determine the natural history of asymptomatic disc abnormalities in magnetic resonance imaging and to identify predictors of future low back pain-related medical consultation and work incapacity. SUMMARY OF BACKGROUND DATA: The natural history of individuals with asymptomatic disc herniations has not been well established, but the high rate of lumbar disc alterations recently detected in asymptomatic individuals by magnetic resonance imaging demands reconsideration of a pathomorphology-based explanation of low back pain and sciatica. METHODS: Forty-six asymptomatic individuals who had a high rate of disc herniations (73%) were observed for an average of 5 years (range, 54-72 months). Four classes of variables (medical data including magnetic resonance imaging-identified disc abnormalities, general psychological factors, physical job characteristics, and psychosocial aspects of work) were assessed at baseline and follow-up. RESULTS: Disc herniations and neural compromise did not significantly worsen at follow-up, whereas disc degeneration progressed in 17 individuals (41.5%). Minor episodes of low back pain occurred in 19 individuals (41.3%), 6 of whom had to seek medical treatment and 5 of whom had to stop work temporarily. The requirement for low back pain-related medical consultation was predicted with high accuracy by listlessness, job satisfaction, and working in shifts (P < 0.001). Work incapacity was best predicted by physical job characteristics, job disaffection, and working in shifts (P < 0.01). CONCLUSION: Physical job characteristics and psychological aspects of work were more powerful than magnetic resonance imaging-identified disc abnormalities in predicting the need for low back pain-related medical consultation and the resultant work incapacity. However,the conclusions are still preliminary, and replication of the findings in larger and more representative study samples is needed.

Adult↗
PubMed2000

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in childhood: a report of ten cases and review of the literature.

UNLABELLED: Chronic recurrent multifocal osteomyelitis is a rare chronic inflammatory musculoskeletal process observed in children and young adults. Recently, the acronym SAPHO syndrome (for synovitis, acne, pustulosis, hyperostosis, osteitis) was coined to emphasise the association between osteo-articular inflammations and different skin abnormalities which are aseptic and filled with neutrophils. In adults, chronic recurrent multifocal osteomyelitis is now a classical manifestation of SAPHO syndrome. Chronic skin disorders were seen in eight of ten children on follow-up at the University Children's Hospitals in Bern and Zurich and in 61 of 260 paediatric cases reported in the literature. The different skin lesions were palmoplantar pustulosis (n = 40), non-palmoplantar pustulosis (n = 6), psoriasis vulgaris (n = 16) or severe acne (n = 4). More rarely Sweet syndrome (n = 2) or pyoderma gangrenosum (n = 1) were reported. CONCLUSION: The synovitis, acne, pustulosis, hyperostosis, osteitis syndrome is pertinent even in paediatrics since skin involvement is frequent.

Acquired Hyperostosis Syndrome↗
PubMed2000

Case series: coexistence of Sjögren's syndrome and sarcoidosis.

OBJECTIVE: To present cases of coexisting sarcoidosis and Sjogren's syndrome (SS). METHODS: We analyzed the clinical data of our 464 patients with SS with a clinical picture suggesting coexisting SS and sarcoidosis. We followed them for several years. RESULTS: We found 5 patients with coexisting SS and sarcoidosis. In 3 patients, pure sarcoidosis could mimic SS. CONCLUSION: In our experience, the frequency of sarcoidosis in SS is much higher than in the general population. One of the European criteria is that before the diagnosis of SS is made, the presence of sarcoidosis must be excluded. From our experience of 5 cases we determined that the 2 diseases can coexist, which indicates the value of these criteria.

Adult↗
PubMed1998

Laparoscopic resection of a bleeding meckel s diverticulum: a case report and review of the literature.

The preoperative diagnosis of Meckel's diverticulum in adults is uncommon, and even more infrequent is the presentation of a bleeding Meckel's diverticulum after childhood. The case of a 22-year old, otherwise healthy male is presented here. The diagnosis was made by barium examination of small bowel and confirmed by diagnostic laparoscopy, followed by complete laparoscopic resection using an Endo-GIA Stapler (United States Surgical Corp., Norwalk, Conn.]. Histopathological examination of the specimen showed inflammed ileal mucosa with hemorrhages in several foci. The literature of Meckel's diverticula and its complications are reviewed here. Based on data from the reviewed literature and our own experience, we suggest that laparoscopic resection is the treatment of choice for Meckel's diverticulum, if it is diagnosed preoperatively or during diagnostic laparoscopy. The procedure allows for a smooth postoperative course, early discharge from the hospital, and arapid return to normal activity.

Journal Article↗
PubMed1998

The role of routine pelvic lymph node sampling in patients with stage I endometrial carcinoma: second thoughts.

BACKGROUND AND METHODS: The cases of 245 patients diagnosed during 1980-1989 with stage I endometrial carcinoma were retrospectively reviewed in order to assess the contribution of lymph node sampling (LNS) to both course of treatment and outcome. The 183 women treated by gyneco-oncologic surgeons had undergone the standard surgical procedure of total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO) and pelvic lymph node sampling (LNS). Sixty-two other women, treated by gynecologists, received only TAH and BSO. Of women who had received TAH+BSO+LNS, 105 (57.4%) were referred for adjuvant radiotherapy on the basis of one or any combination of high grade histology (G2 or G3), myometrial invasion to a depth of 50% or more and LNS positivity. Of the group who had not had LNS, 37 (59.7%) likewise received adjuvant radiotherapy but on the bases of histology and/or depth of invasion. RESULTS AND CONCLUSIONS: Recurrence and survival over a mean follow-up period of 7.5 years (range 5-15 years) showed no significant differences between the patients who underwent LNS and those who did not. Of 43 recurrences, six were among 'low risk' women (those with both minimal invasion and low grade histology), suggesting a special need among this group for the additional staging information which LNS may provide.

Carcinoma↗
PubMed1997

Opposing effects of tyrosine kinase inhibitors on mineralization of normal and tumor bone cells.

Induction of matrix maturation and mineralization in calcified tissues is important for patients with primary bone tumors and other bone deficiencies, e.g., osteoporosis. For the former it signifies a better prognosis in osteosarcoma, and for the latter it might improve bone remodeling. In the present study we exposed osteosarcoma cells (Saos2), normal bone cells, and marrow stroma to two different tyrosine kinase (TK) inhibitors: AG-555 and AG-1478. These tyrphostins differ in their effect on signal transduction downstream to the TK receptor (RTK): AG-1478 inhibits src family TKs whereas AG-555 inhibits nuclear TKs. We found that both tyrphostins at 50 microM increased specific alkaline phosphatase (ALP) activity in Saos2 cells. AG-555 abrogated mineralization whereas AG-1478 increased it. Similarly, in human bone-derived cell cultures the same dose of tyrphostins had an opposing effect on mineralization but, in contrast to AG-555, AG-1478 positively selected cells with ALP activity. These tyrphostins also differed in their effect on rat marrow stromal cells. AG-555 decreased cell counts unselectively, whereas the decreased cell counts by AG-1478 resulted in selection of osteoprogenitor cells as indicated by a concordant increase in specific ALP activity. The effect of a lower dose of AG-1478, 5 microM, on the increase in mineralization exceeded its own efficiency in selecting cells with specific ALP activity. Our results indicate that AG-1478 selects and preserves the osteoblastic phenotype, at doses moderately higher than those required to induce mineralization, and substantially higher than the doses required for RTK inhibition. Identification of downstream molecular targets for AG-1478, in marrow stromal cells, might prove useful in designing more selective drugs, capable of separating proliferative from differentiation-inducing activities.

Alkaline Phosphatase↗
PubMed1997

Cyclosporin A and its non-immunosuppressive derivative exhibit a differential effect on cell-mediated mineralization in culture.

Chronic immunosuppressive treatment with cyclosporin A (CsA) is associated with decreased bone density. However, in culture, CsA inhibits osteoclast differentiation and bone resorption. This raises the question as to whether CsA also affects osteoblast function. Immunophilin, one of the CsA-binding cyclophilins that is implicated in the immunosuppressive action of CsA via calcineurin, is a peptidyl prolyl cis-trans isomerase (PPl). CsA also binds a mitochondrial membrane PPl which is implicated in controlling permeability transition pores. Therefore, in the present study we tested the effect of CsA on cell mediated mineralization in parallel with mitochondrial rhodamine retention as an indicator of mitochondrial membrane potential Rat marrow stromal cells were grown in dexamethasone (DEX) medium to stimulate mineralization in culture, and CsA was added to various cultures using different treatment schedules. Low dose (0.1 microM) CsA inhibited mineralization, compared to controls, when present in the cultures during days 3-11 of DEX stimulation. Contrarily, high dose CsA (1.0 microM) resisted the inhibitory effect of the low dose. SDZ 220-384 (SDZ), a non-immunosuppressive derivative of CsA which is known, like CsA, to bind to mitochondrial cyclophilin but does not inhibit calcineurin, was also tested. Both high and low doses of SDZ decreased mineralization when present in the cultures from day 3 or from day 0. The similar effect of the low CsA dose and SDZ on mineralization is in accord with their ability to block permeability transition pores. The differential effect, on day 21 mineralization, between high CsA dose and SDZ took place in parallel to their opposing effects on mitochondrial membrane potential. On days 4-8, mitochondrial rhodamine retention was higher under CsA than under SDZ. Under these conditions there was no significant difference between the effects of these drugs on cell proliferation measured on day 11; there was a minor decrease in specific alkaline phosphatase activity by SDZ, too small to explain the extent of mineralization inhibition by SDZ. These results suggest that permeability transition pores might be involved in controlling mineralization. Unlike SDZ, CsA exhibits an additional effect on the mitochondrial membrane potential and on mineralization when applied at a high dose on day 3. Therefore identifying the additional activity of high dose CsA, which is missing in SDZ, may be beneficial. Such activity is expected to resist changes in rhodamine retention and decreased mineralization induced by SDZ, and yet enable preservation of immunosuppressive activity of CsA.

Alkaline Phosphatase↗
PubMed1996

Cell-mediated mineralization in culture at low temperature associated with subtle thermogenic response.

In both the growth plate and in marrow stromal cell cultures cell-mediated mineralization is preceded by characteristics of anaerobic and low efficiency energy metabolism. Reagents that increase mineralization like malonate and dexamethasone (DEX) also increase the mitochondrial membrane potential (MtMP) especially 1 week after DEX stimulation. Contrarily, levamisole, which decreases mineralization, also decreases MtMP. Modulation of MtMP and energy metabolism could be linked to regulation of mineralization by the uncoupling of oxidative phosphorylation. This uncoupling should be associated with thermogenesis in cells that induce mineralization. We examined whether cold temperature affects mineralization, and whether cellular thermogenesis takes place at cold temperature in parallel to changes in MtMP. Osteoprogenitor cells (OPC) induced, in DEX stimulated rat marrow stroma, higher mineralization at 33 degrees C than at 37 degrees C. Increased mineralization by cold temperature required long incubation since incubation in the cold during short intervals, 3-4 days, did not increase mineralization relative to (37 degrees C) controls. Marrow stromal cells in the presence of valinomycin responded to incubation at 33 degrees C by retaining all the vital dye after 4 h, unlike the cells at 37 degrees C; however, after 24 h the level of dye retention at 33 degrees C was the same as at 37 degrees C. The delayed response of the temperature-dependent (> 37 degrees C) K+ ionophor to incubation in the cold indicated that certain cells may respond to low temperature by local intracellular heating, and by heat conduction to the plasma membrane. DEX-stimulated stromal cells, unlike unstimulated cells, showed increased mitochondrial rhodamine 123 retention in the presence of valinomycin after 24 h in the cold, which corresponds to day 4 of OPC induction. This is consistent with the concept that valinomycin-induced cell damage is mediated by (cold-induced) local heating. The mechanism of this cell damage should selectively prefer nonthermogenic (rhodamine retaining) over thermogenic (rhodamine leaking) cells such as OPC. At cold temperature DEX-stimulated stromal cells showed the best anti-OPC selection under exposure to valinomycine between days 3-7, concurrent with the period of rhodamine leakage from the mitochondria. These results indicate that thermogenesis is enhanced during the period of low MtMP in mineralizing cells, and prolonged exposure to cold increases mineralization also due to induction of subtle thermogenesis.

Animals↗
PubMed1996

Opposing effects on mitochondrial membrane potential by malonate and levamisole, whose effect on cell-mediated mineralization is antagonistic.

The act of chondrocyte preparation for primary, enchondral, mineralization is associated with a decline in mitochondrial respiration toward the end of the proliferative zone and the hypertrophic zone in the growth plate. Dexamethasone (Dex)-stimulated cultures of rat marrow stroma constitute a differentiation model simulating, in its energy metabolism, chondrocyte mineralization. In this model, early inhibition of succinate dehydrogenase (SDH) enriches the culture with mineralizing cells, whereas levamisole inhibits mineralization. Dex also increases mitochondrial membrane potential in stromal cells, especially on days 7-8 of stimulation. In the present study, suicide inhibition of SDH, by nitropropionic acid (NPA), in Dex-stimulated cells showed a dose-dependent increase in day 21 mineralization; the maximal effect was induced on days 2-4 of stimulation. Mineralization under 2-day-long exposure to NPA showed a similar trend to the previously studied effect of continuous exposure to malonate applied between days 3-11. Unlike malonate, the effect of NPA required its presence in the cultures for only 2 days and resulted in higher mineralization than that seen under 8 days of malonate. NPA delineated a period, days 2/4 to 7/9, in which inhibition of succinate oxidation is necessary to augment mineralization. During this period, NPA also exhibited OPC selection capacity. Early application of levamisole, under conditions previously shown to decrease day 21 mineralization, maintained mitochondrial membrane potential at the beginning of Dex stimulation but decreased or had little effect on it during days 5-10. By contrast, malonate previously found to increase day 21 mineralization decreased the membrane potential at the beginning of Dex stimulation but increased it later on day 7, or during days 5-10. These results indicate that during osteoprogenitor differentiation, before the mineralization stage, a surge in mitochondrial inner membrane potential during late matrix maturation may be a marker that heralds the extracellular matrix mineralization.

Alkaline Phosphatase↗
PubMed1996

Blunt hepatic trauma in adults: correlation of CT injury grading with outcome.

PURPOSE: To correlate injury grading with computed tomography (CT) to treatment outcome. MATERIALS AND METHODS: Forty-eight patients with proved blunt hepatic injuries underwent dynamic CT with contrast material before treatment. The injuries were classified with a five-point CT-based grading system. The CT injury grades and the amount of hemoperitoneum seen on CT scans were compared with the clinical and surgical findings, radiologic follow-up, and outcome. RESULTS: Hepatic injuries were classified as CT grade 1 in two patients, grade 2 in 15 patients, grade 3 in 21 patients, and grade 4 in 10 patients. Conservative treatment was performed in 38 patients, including 15 patients with grade 3 and 10 patients with grade 4 injuries; 10 of these patients also had major hemoperitoneum (> 500 mL). Conservative treatment was successful in 37 patients but was complicated in two patients by development of an arteriovenous fistula or a biloma and failed in one patient because of delayed hepatic rupture. Exploratory laparotomy was performed in 10 patients but revealed marked active hepatic bleeding in only one patient. CONCLUSION: Injury grading with CT may reflect the degree of hepatic parenchymal damage but does not indicate patients in whom complications may develop or surgery is necessary. Monitoring of conservative treatment with CT allows detection of resultant complications.

Adult↗
PubMed1995

Analysis of cell-mediated mineralization in culture of bone-derived embryonic cells with neurofibromatosis.

von Recklinghausen neurofibromatosis (NF1) is an autosomal dominant genetic disorder associated with congenital pseudoarthrosis and with short stature. To examine whether the NF1 phenotype includes functional osteogenic defects, embryonic bone-derived cells affected with NF1 were tested in culture for specific alkaline phosphatase (ALP) activity and cell-mediated mineralization and compared with other embryonic bone derived cells. NF1 showed a relatively higher specific ALP activity, which has further increased in response to dexamethasone + beta-glycerophosphate (beta GP) (Dex medium) coordinately with a decrease in cell proliferation. In In the control group, two samples showed increased ALP activity, one showed decreased activity and the forth one did not show any change in ALP. NF1 cells were distinguished from other cells regarding day 21 mineralization, they did not mineralize when cultured with ascorbate alone in the absence of Dex medium, whereas control cells did mineralize. Adding beta GP resulted in mineralization by NF1 cells but less than in other cells. In addition, NF1 cells responded to dexamethasone by increasing the beta GP-induced mineralization, as opposed to cells from other embryonic bones, which either did not respond or have even decreased mineralization under dexamethasone. Upon cis-hydroxyproline exposure, Dex medium has also distinguished NF1 cell ALP activity from that of other cell origins. Inhibition of respiratory complex II by malonate showed that most embryonic bone-derived cells of 12 weeks gestation are malonate resistant; thus, malonate selection was ineffective. This is in contrast to rat marrow stromal cells previously shown to undergo mineralizing cell enrichment in response to malonate. Exposure to levamisole, of Dex-treated cells, at days 0-11 has inhibited day 21 mineralization in all tested cultures in spite of the increase in day 11-specific ALP activity. Both malonate and levamisole did not distinguish NF1 cells from the osteogenic phenotype of other cells. Essentially embryonic bone-derived cells from 12 weeks gestation, cultured in the absence of beta GP, retained their mineralization capacity, which does not increase under dexamethasone, as distinguished from NF1 cells which require beta GP for mineralization and positively respond to dexamethasone. Therefore, bone-derived NF1 cells may be useful for studying the regulation of the mineralization process.

Alkaline Phosphatase↗
PubMed1995

Tibial implant mineralization in rats is inversely related to serum osteogenic capacity.

In this study, the correlation between the mineralization of healing bone defects and the osteogenic capacity of the serum was tested in rats. The purpose of the study was to test the hypothesis that during callus formation, some serum factors are consumed. The bone defects in the tibia contained two different implant types, and all sustained juxta-implant fractures. One implant type was the coral Porites and the other was its recrystallized version (Interpore-200), which exhibit different mineralization rates during fracture healing. Use of these two implant types permitted generation of an expanded mineralization spectrum suitable for regression analysis. Mineralization was assessed by measuring the mineral content change (MCC) using dual-energy X-ray absorptiometry. Osteogenic capacity of sera of the implanted rats was assessed by its ability to increase specific alkaline phosphatase (ALP) activity in stromal cell cultures. The MCC was followed for 5 weeks in the Porites and Interpore-200 implants, and it was found that the MCC in Interpore-200 implants exceeded that of the Porites implants. Thus, the two implant types generated a wide mineralization spectrum. Induction of ALP in stromal cell culture was lower for sera derived from rats implanted with Interpore-200 than for sera derived from rats implanted with Porites. Two weeks after implantation, the change in serum ALP induction correlated inversely with the MCC of bone defects. This indicates that during callus formation, the mineralization rate is reciprocally related to the serum osteogenic capacity. The decreased serum osteogenic capacity may be interpreted by the hypothesis that callus formation consumes certain serum osteogenic factors.

Alkaline Phosphatase↗
PubMed1994

Marrow stromal cell commitment to mineralization under the effect of a prolyl hydroxylase inhibitor.

Mitochondrial response to the effect of a hydroxylase (PH) inhibitor was tested in marrow stromal cells during stimulation of osteoprogenitor cell (OPC) differentiation. The rationale for this was to explore pathways of regulatory interactions between procollagen synthesis and mitochondrial respiration that could be linked to the commitment of OPCs to mineralization. Stimulated OPCs exposed to the PH inhibitor cis-hydroxyproline (cis-HP), compared to the noninhibiting isomer trans-HP, for 11 days showed a dose-dependent decrease in cell proliferation, the surviving cells showed increased alkaline phosphatase activity. Trans-HP did not influence the cis-HP effect on ALP and on proliferation arrest. Short time exposures, 2-3 days, to cis-HP at different periods suggested that Days 0-3 and 3-5 were critical for the commitment to Day 21 mineralization of OPCs. On Days 0-3 cells were most sensitive to cis-HP, since on Day 11, 8 days after removal of cis-HP, they were too scarce to be counted by the staining method. However, the presence of 5.0 mM cis-HP in the cultures during Days 3-5 has induced on Day 21 close to 24-fold more mineralization/cell than controls, compared to the trans-HP effect, which was only close to 3-fold. The presence of cis-HP in the cultures on Days 0-3 has augmented the mitochondrial Day 3 retention of rhodamine 123 (Rho) in the stromal cells, relative to controls, compared to the presence of trans-HP. However, the presence of cis-HP during Days 3-5 or 3-6 resulted in lower Day 5 Rho retention, relative to controls, which was not significantly different from the retention that resulted from trans-HP. Since Rho retention is related to the final result of aerobic respiration level, these results are interpreted as a cis-HP inhibitory effect on procollagen peptidyl-proline hydroxylation, which may in turn release oxygen surpluses, to be available for mitochondrial consumption. The fall in Rho retention responses to cis-HP between Days 0-3 and 3-5 is suggesting either abrupt decrease in proline hydroxylation or poor mitochondrial sensitivity to oxygen in Day 3-5 cultures.

Alkaline Phosphatase↗