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Biomedical subjects

J Sandbank

Publications and source records attributed to J Sandbank.

At least 19 recordsLinked to original sources
PubMed2006

Dextran 40 (Rheomacrodex) or Polygeline (Haemaccel) as an epidural patch for post dural puncture headache: a neurotoxicity study in a rat model of Dextran 40 and Polygeline injected intrathecally.

BACKGROUND AND OBJECTIVE: Although an epidural autologous blood patch is considered the most effective treatment for post dural puncture headache, which sometimes occurs following spinal or inadvertent spinal anaesthesia, there remains a need for alternative materials for epidural patches. We investigated the potential neurotoxicity of Dextran 40 (Rheomacrodex) and Polygeline (Haemaccel) used for this purpose in a rat model. METHODS: Repeated boluses of 10% Dextran 40, 3.5% Polygeline or 0.9% saline were injected intrathecally over a period of 1 month in three groups of rats. RESULTS: No behavioural or clinical derangements were observed in any of the three groups during this period. After sacrifice of the animals at the end of the experiment, no significant differences in the histopathological appearances of the spinal cords in the three groups were observed. No toxic effects diminishing viability of spinal cord cells were evident. Similarly, viability of renal, hepatic and peripheral blood mononuclear cells remained unaffected (98% +/- 2%). CONCLUSIONS: No deleterious effects, clinical or cellular, were evident in this rat model when Dextran 40 or Polygeline were injected intrathecally. Thus, both substances can be considered as possible alternative materials for epidural patches.

Animals↗
PubMed2005

Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines.

Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits phosphorylation of downstream proteins involved in BCR-ABL signal transduction. It has proved beneficial in treating patients with chronic myeloid leukaemia (CML). In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. In the light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on telomerase activity (TA) and regulation in various malignant cell lines. Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK-MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No apoptosis was observed. Inhibition of TA was caused mainly by post-translational modifications: dephosphorylation of AKT and, to a smaller extent, by early downregulation of hTERT (the catalytic subunit of the enzyme) transcription. Other steps of telomerase regulation were not affected by IM. This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation.

Animals↗
PubMed2003

Isolated bone marrow non-Hodgkin's lymphoma. Report of two cases and literature review.

We report two patients with isolated bone marrow non-Hodgkin's lymphoma and we review the additional 23 cases thus far described. Bicytopenia or pancytopenia and an elevated erythrocyte sedimentation rate were universally present. Some 84% of the patients manifested fever of unknown origin (FUO), 64% constitutional symptoms, 48% hepatomegaly, and 52% splenomegaly. Of the variety of therapeutic protocols used, corticosteroids, alone or in combination, appeared to be the most effective. Survival ranged from 1 week to 4.5 years. Early diagnosis would avoid unnecessary work-up in patients with FUO and enable optimization of therapy.

Journal Article↗
PubMed2002

Breast hamartomas: clinicopathological and immunohistochemical studies of 24 cases.

AIMS: The aim of our study was to investigate the clinical, pathological and immunohistochemical features of breast hamartomas, in order to obtain a detailed profile of this somewhat uncommon lesion. METHODS AND RESULTS: This study presents a clinical, pathological and immunohistochemical analysis of 24 breast hamartomas. Four cases of fibrocystic breast changes were used as a control group. The immunohistochemical panel induced oestrogen (ER) and progesterone (PR) receptors, c-erbB-2 protein, p53, Ki67, CK-MNF116, and vimentin. The patients ranged in age from 30 to 78 years (mean 48 years). All patients presented with a palpable unilateral mass. Three patients showed two hamartomas in the same breast. Tumours ranged from 20 to 50 mm in diameter. Typical macroscopic and microscopic features were noted. Immunohistochemical studies showed ER and PR receptor positivity in epithelial cells as well as in the stromal cells in all 24 cases. No c-erbB-2 protein over-expression was noted. p53 expression was not observed. Ki67 showed 2-3% positivity in epithelial cells and not in stromal cells in most cases. CONCLUSIONS: There was no association with side, ethnic origin or dietary habits. The immunohistochemistry of hamartomas is generally similar to normal breast or fibrocystic breast tissue. Ki67 together with receptor positivity may reflect some proliferative activity and explain observed faster growth of hamartoma during pregnancy and lactation.

Adult↗
PubMed2002

Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma.

AIMS: To find a possible correlation of Ki67 antigen and proliferating cell nuclear antigen (PCNA) with prognosis in anorectal malignant melanoma. METHODS AND RESULTS: Thirty patients with anorectal malignant melanoma were studied. The percentage of tumour cells stained for Ki67 and PCNA in paraffin sections was assessed. Mode of treatment (local excision or abdominoperineal resection), depth of tumour invasion, attempt at cure as defined by complete tumour excision and absence of distant metastases at presentation, tumour blood vessel invasion, and tumour necrosis, as well as Ki67 and PCNA, were all correlated with survival. By univariate analysis, PCNA, Ki67, attempt at cure, local excision (and not abdominoperineal resection), and depth of invasion were all significantly associated with longer survival. By multivariate analysis, only PCNA was significantly associated with survival, while Ki67 showed a significant positive correlation with PCNA. With a cut-off point of 40%, patients with lower Ki67 scores showed survival advantage over those with higher Ki67 scores (P=0.0004). With a cut-off point of 80%, patients with lower PCNA scores showed survival advantage over those with higher PCNA scores (P=0.0001). The staining for proliferation markers was also associated with depth of tumour invasion. CONCLUSIONS: Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.

Aged↗
PubMed2002

Antenatal sonographic diagnosis of testicular torsion.

Antenatal testicular torsion is a well-established condition diagnosed and treated after birth. This report describes the antenatal diagnosis of testicular torsion with surgical and pathological confirmation. Antenatal and postnatal sonographic findings included enlarged testis and epipdidymis surrounded by hemorrhagic fluid organized in two concentric compartments ('double ring hemorrhage' image). A contralateral hydrocele with bulging of the scrotal septum towards the unaffected side were also present. Pathological examination demonstrated a recent extravaginal torsion, which is the predominant mechanism for testicular torsion in the fetus and neonate. Recognition of this phenomenon and the ultrasonographic images associated with it may enable the diagnosis of antenatal testicular torsion to be made on prenatal sonography of the fetus.

Adult↗
PubMed2002

Transient bone oedema of the tibia mimicking a tumorous process.

The authors describe a distinct clinical entity consisting of bony tenderness, increased isotope uptake along the metaphyses and/or diaphyses and magnetic resonance changes simulating a bone marrow-replacing lesion. Bone biopsies indicate the presence of bone marrow fibrosis and some new bone formation. Nine such cases were prospectively evaluated according to a standardized protocol including clinical examination, x-rays, bone scan and CT scan as well as MRI scans including contrast medium injection. All patients presented with tibial tenderness. In one case the bone was noticeably thicker as compared to the other side. The ages ranged from 6 years to 64 years and 6 of the patients were female. Xrays were normal in 6/9 patients; the rest had minimal periosteal reaction, and mild intramedullary sclerosis. Uniform imaging findings were longitudinal increased uptake along the metadiaphysis of the tibia on bone scans, and increased bone marrow density on CAT scans without a fracture line. A magnetic resonance study indicated bone marrow replacement as demonstrated by an area of low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Some enhancement of signal was observed following gadolinium injection. This clinical entity, which the authors attribute to be a medullary stress reaction, is self-limited, and pain resolves within 3 months. However the radiographic changes appear to be permanent. A biopsy is not required provided no cortical penetration or soft tissue mass is demonstrated by MRI scan.

Adolescent↗
PubMed2001

Red eye syndrome: clinical and experimental experience in a new aspect of diffuse eosinophilic infiltration?

Twenty-two of 24 hemodialysis patients dialyzed simultaneously with a new batch of cellulose acetate dialyzers promptly developed a spectrum of symptoms and physical signs including red eyes, hearing loss, tinnitus, and bone pain, previously described as red eye syndrome. We subsequently injected 4 rabbits with an eluate from a dialyzer of the same or a control batch. Six hours following exposure, the animals developed, in addition to red eyes, diffuse eosinophilic infiltration of various organs as well as myopathic changes and moderate brain edema. On the basis of these data, we suggest that it cannot be concluded whether the underlying pathophysiological mechanisms were toxic, allergic or both and that the occurrence of relevant symptomatology in 2 or more simultaneously dialyzed patients is a strong argument against unnecessary diagnostic or therapeutic procedures. Finally, a second exposure in a given patient should be avoided.

Animals↗
PubMed2001

Double-blind randomized study evaluating regeneration of the rat transected sciatic nerve after suturing and postoperative low-power laser treatment.

This double-blind randomized study evaluated the therapeutic effect of low-power laser irradiation (LPLI) on peripheral nerve regeneration, after complete transection and direct anastomosis of the rat sciatic nerve. After this procedure, 13 of 24 rats received postoperative LPLI, with a wavelength of 780 nm laser, applied transcutaneously, 30 min daily for 21 consecutive days, to corresponding segments of the spinal cord and to the injured sciatic nerve. Positive somatosensory evoked responses were found in 69.2 percent of the irradiated rats (p = 0.019), compared to 18.2 percent of the non-irradiated rats. Immunohistochemical staining in the laser-treated group showed an increased total number of axons (p = 0.026), and better quality of the regeneration process, due to an increased number of large-diameter axons (p = 0.021), compared to the non-irradiated control group. The study suggests that postoperative LPLI enhances the regenerative processes of peripheral nerves after complete transection and anastomosis.

Animals↗
PubMed2001

Structural modification and cryopreservation of porcine heart valves for xenotransplantation with reduced immunity.

BACKGROUND AND AIM OF THE STUDY: In order to provide valved xenografts with reduced immunity, yet durability comparable with that of homografts, a method for endothelial cell removal was developed. METHODS: Adult porcine valved pulmonary conduits were isolated, washed and incubated in trypsin-EDTA solution. The endothelial cells were flushed free with a stream of culture medium, and the xenografts cryopreserved. Grafts were thawed after three months, and evaluated structurally. RESULTS: Macroscopic inspection of the grafts revealed no cracks or other morphological damage. Light microscopy revealed mildly edematous changes, and the elastic layers appeared to be preserved. Incubation with trypsin-EDTA solution consistently removed the entire endothelial layer, without obvious damage to the underlying tissues. CONCLUSION: With care and appropriate timing, the xenograft endothelium can be selectively removed, leaving the underlying tissue intact. This process may allow further structural manipulations to improve the durability of these grafts.

Animals↗
PubMed2001

[Primary gastrointestinal stromal tumors].

UNLABELLED: Stromal tumors of the GI tract are rare. In the retrospective and prospective study we investigated the relationship between tumor symptomatology, tumor grade and prognostic factors. During the period May 1993-September 1999, 11 female and 13 male patients with a mean age of 62 (range-29-81) years were operated for primary gastrointestinal stomal tumors (GIST) in our department. Observed signs and symptoms were: GI bleeding (65%), abdominal pain (45%), abdominal mass (15%) and weakness (5%). In 4 patients tumor was an incidental finding during investigation or operation for another tumor. Tumor location (in decreasing order) was: stomach (15), small bowel (SB, 6), esophagus (1), duodenum (1) and colon (1). Preoperative biopsy or FNA were diagnostic in less than 50% of the cases. Operative procedures included wedge resection (8 patients), resection of segment of bowel (10) and extended resection (6), of diaphragm, SB, colon, bladder, kidney and liver. The mean tumor size was 7.8 (range-0.9-22) cm. Four tumors were graded as benign, 8 of indeterminate malignant potential and 12 malignant. CONCLUSION: The main presentation of GIST is acute GI bleeding. Endoscopy is most effective for studying proximal tumors, and CT should be used to identify distal GI tract tumors. Tumor size or malignancy were not necessarily predictive of GI bleeding. When invasive to adjacent organs is present, wide excision should be contemplated as long-term survival can be achieved.

Adult↗
PubMed2001

[Epidemiological characteristics and I-131 scintigraphic of patients with papillary thyriod carcinoma with distant metastases].

One hundred and twenty-nine patients with papillary thyroid carcinoma were treated with radioiodine (I-131) and followed up in our department between the years 1992 and 2000. Thirty-three patients (25.6%) had distant metastases (mean follow-up time was 3.12 +/- 2.9 years). The incidence of distant metastases among patients with papillary carcinoma was higher in our group in comparison with most published studies. The most common sites for distant metastases were the lungs and mediastinum. In 32 of the 33 patients distant metastases were found in those sites. We characterized two main patterns of I-131 uptake in lung metastases: in the first there was diffuse lung uptake and in the second there were focal lesions. Bone metastases were only found in one patient. Distant metastases were found in 38.7% of males as compared to 21.4% of females. The age of the male patients with distant metastases was significantly higher than the age of the other patients (mean age 52.8 years, p = 0.099). There was no significant association between distant metastases and advanced age. Most cases of distant metastases in females (81%) were diagnosed at the time of the primary diagnosis as compared to less than half (42%) in males. Sixteen patients with distant metastases underwent cervical lymph node dissection. In 15 patients (94%) cervical lymph node metastases were found. It was found that 39.4% of the patients with distant metastases were born in Israel and 30.3% were born in the Soviet Union. The percentage of the patients with distant metastases, who came to Israel from the Soviet Union after the nuclear accident in Chernobyl (1986), was found to be significantly higher then their relative number in the Israeli population and higher then their relative number in the hospitalized patient population in the years of the study (24.2% as compared to 9% and 8.1% respectively). The survival rate of patients with distant metastases was 97% and for patients without metastases the rate was 100%.

Adenocarcinoma, Papillary↗
PubMed2000

Clinicopathologic study and classification of vocal cord cysts.

Cysts of the true vocal cords are less common than other laryngeal cysts. They are usually easily recognized and managed. Patients present with complaints of hoarseness and/or dyspnea. We report our experience with 41 cases of cysts located in the true vocal cords. Clinical and histological aspects are reviewed and discussed. A new histological classification is proposed: A: cysts lined by columnar epithelium with mucous content; B: lined by columnar epithelium with cilia; C: lined b squamous epithelium without keratinization; D: lined by squamous epithelium with keratinization.

Adult↗
PubMed2000

Expression of the p53 gene and apoptosis in gestational trophoblastic disease.

In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P< 0.0003 and P< 0.004, respectively). In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apoptosis to modulate excessive trophoblastic proliferation.

Apoptosis↗
PubMed2000

Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function.

The chemokine stromal-derived factor-1 (SDF-1) controls many aspects of stem cell function. Details of its regulation and sites of production are currently unknown. We report that in the bone marrow, SDF-1 is produced mainly by immature osteoblasts and endothelial cells. Conditioning with DNA-damaging agents (ionizing irradiation, cyclophosphamide, and 5-fluorouracil) caused an increase in SDF-1 expression and in CXCR4-dependent homing and repopulation by human stem cells transplanted into NOD/SCID mice. Our findings suggest that immature osteoblasts and endothelial cells control stem cell homing, retention, and repopulation by secreting SDF-1, which also participates in host defense responses to DNA damage.

Animals↗