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Biomedical subjects

A Segal

Publications and source records attributed to A Segal.

At least 19 recordsLinked to original sources
PubMed2002

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma.

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.

Aged↗
PubMed2002

[Retinal vein occlusion and carotid Doppler imaging].

PURPOSE: To investigate retinal vein occlusion with B-mode ultrasonography carotid and color Doppler imaging. METHODS: In 223 patients (225 eyes) presenting with retinal vein occlusion, we retrospectively investigated vascular risk factors (hypertension, diabetes, hyperlipidemia, cardiovascular history, smoking, and glaucoma), standard laboratory tests, and color Doppler imaging of the carotid artery. RESULTS: The data from 106 women (47.54%) and 117 men (52.46%), with a mean age of 65 years, were studied, with 169 patients presenting a central retinal vein occlusion (CRVO) and 56 a branch retinal vein occlusion (BRVO). Thirteen patients (6%) had significant carotid artery stenosis (>=70%), which was the single etiology. Forty patients (18%) had nonsignificant carotid artery stenosis (<70%) with a risk of embolism production. Such carotid artery lesions found in color Doppler imaging in the RVO investigations were significantly more frequent in older patients (>65 years) who presented at least two RVO risk factors (p<0.001). CONCLUSION: This study has shown the the advantages of carotid Doppler imaging in retinal vein occlusion.

Adult↗
PubMed2001

Functional integrity of the vesicle transporting machinery is required for complete activation of cFTR expressed in xenopus laevis oocytes.

We expressed the human cystic fibrosis transmembrane conductance regulator (CFTR) in oocytes of the South African clawed frog Xenopus laevis. We performed simultaneous and continuous recording of membrane current (Im), conductance (Gm) and capacitance (Cm), the latter being a direct measure of membrane surface area. A cAMP-cocktail containing cAMP and isobutylmethylxanthine (IBMX) increased all parameters, demonstrating that CFTR activation was partly achieved by exocytotic delivery and insertion of preformed CFTR molecules into the plasma membrane. CFTR currents after cAMP-cocktail were correlated with the capacitance of the oocytes: oocytes with larger Cm exhibited larger currents. Expression of CFTR itself did not change the Cm of the oocytes. However, activation of CFTR with cAMP-cocktail increased Im and Gm 15- and 20-fold, respectively while membrane surface area increased by about 7%, indicating the functional insertion of preformed CFTR into the plasma membrane. While cAMP-cocktail yielded maximal CFTR stimulation, IBMX alone, but not caffeine or theophylline, was sufficient to stimulate more than half of the increases in Im and Gm as observed with cAMP-cocktail. Since Cm was not significantly stimulated by IBMX, we conclude that IBMX alone activated the CFTR channels already present in the oocyte membrane. CFTR stimulation by cAMP-cocktail was independent of external Ca2+ and ATP had no additional activating potency. The role of protein trafficking in the activation of CFTR evoked by increases of cytoplasmic cAMP was assessed by measuring the effects of brefeldin A (BFA), nocodazole and primaquine on the bioelectric parameters and membrane surface area. All these compounds that interfere with the protein trafficking machinery at different stages prevented the translocation of CFTR from intracellular pools to the plasma membrane. These data confirm and extend our previous observations that CFTR expressed in Xenopus laevis oocytes is activated via dual pathways including direct activation of CFTR already present in the membrane and exocytotic insertion of preformed CFTR channels into the membrane. Furthermore, we show that complete activation of CFTR requires an intact protein trafficking machinery.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Different activation mechanisms of cystic fibrosis transmembrane conductance regulator expressed in Xenopus laevis oocytes.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP sensitive Cl- channel that is defective in cystic fibrosis (CF). The most frequent mutation, namely deltaF508-CFTR, accounts for 66% of CF. Here we show that cAMP-activation of CFTR occurs via at least two distinct pathways: activation of CFTR molecules already present in the plasma membrane and protein kinase A (PKA)-mediated vesicular transport of new CFTR molecules to the plasma membrane and functional insertion into the membrane. We investigated the mechanisms that are responsible for these activation pathways using the Xenopus laevis oocytes expression system. We expressed CFTR and recorded continuously membrane current (Im), conductance (Gm) and capacitance (Cm), which is a direct measure of membrane surface area. Expression of CFTR alone did not change the plasma membrane surface area. However, activation of CFTR with cAMP increased Im, Gm and Cm while deltaF508-CFTR-expressing oocytes showed no response on cAMP. Inhibition of protein kinase A or buffering intracellular Ca2+ abolished the cAMP-induced increase in Cm while increases of Im and Gm were still present. ATP or the xanthine derivative 8-cyclopentyl-1,3-dipropylxanthine (CPX) did not further activate CFTR. Insertion of pre-formed CFTR into the plasma membrane could be prevented by compounds that interfere with intracellular transport mechanisms such as primaquine, brefeldin A, nocodazole. From these data we conclude that cAMP activates CFTR by at least two distinct pathways: activation of CFTR already present in the plasma membrane and exocytotic delivery of new CFTR molecules to the oocyte membrane and functional insertion into it.

Adenosine Triphosphate↗
PubMed2001

Ethnic differences in colorectal cancer among Arab and Jewish neighbors in Israel.

OBJECTIVES: Migrant studies indicate that the differences in the incidence of colorectal cancer (CRC) are probably environmental and not genetic. There is epidemiological documentation that Israeli-born Arabs have much less CRC than Israeli-born Jews. We investigated these differences among Jews and Arabs living within the same central coastal region in Israel. METHODS: The files of pathology-diagnosed patients with CRC hospitalized from 1988 to 1996 were reviewed, and demographic data and incidence and location of malignancies were retrieved for this relative frequency study. RESULTS: Of the 527 patients (51.4% men) diagnosed as having CRC, 489 (92.8%) were Jews and 38 (7.2%) were Arabs (p < 0.001), representing 0.46% and 0.04% of the respective populations in the region. The average age at disease diagnosis of the Jews was 73.8 yr and that of the Arabs 61.4 yr (p < 0.001). Both groups shared identical health facilities and habits of attending them. The Arab patients were or had been employed in occupations that involved more physical activity. The site of lesion was on the right colon in 24.9% of all the cases-23.5% of the Jewish patients and 42.1% of the Arab patients (p < 0.001). Rectal cancer was found in 25.7% of the former and 15.8% of the latter (p < 0.001). CONCLUSIONS: The lower incidence of CRC among the Arabs persisted over time, and that group had greater right side and lesser rectal involvement than their Jewish neighbors, possible indications of genicity. The incidence of CRC among the Jews rose concomitantly with "Westernization" of their lifestyle, supporting a role for environmental influences.

Adult↗
PubMed2001

Acupuncture treatment for irritable bowel syndrome. A double-blind controlled study.

BACKGROUND/AIM: Irritable bowel syndrome is one of the most common gastrointestinal disorders in Western society, affecting around 15% of the population, especially young adults. The cause(s) of irritable bowel syndrome and effective treatment(s) have remained elusive. This study aimed at exploring the therapeutic value of acupuncture by comparing the responses of irritable bowel syndrome sufferers to true acupuncture versus sham acupuncture in a controlled double-blind study. METHODS: Twenty-five patients who fulfilled the Rome criteria (irritable bowel syndrome symptoms persisting for more than 1 year) comprised the final study population. They were recruited through a 'call for' bulletin sent to gastroenterologists practicing in the region of our medical center. True acupuncture was performed at LI-4 (colonic meridian, needle only) and sham acupuncture at BL-60 (urinary vesicle meridian, needle only). Patient assignment to one of the two groups was random. RESULTS: The effect of the first true acupuncture on overall symptoms and abdominal pain was a clear and significant improvement (p = 0.05). No comparable effect was seen in the second session. CONCLUSIONS: Although the true acupuncture results were consistently better, no difference was found between the two groups in the overall statistical analysis. We could not show a therapeutic benefit of this treatment modality in irritable bowel syndrome.

Abdominal Pain↗
PubMed2001

[Tolerance of orbital implants. Retrospective study on 14 years].

UNLABELLED: The authors report the results of enucleations performed from 1985 to 1998 and the different orbital implants used. MATERIAL AND METHODS: All patients undergoing enucleation from 1985 to 1998 were studied. RESULTS: 68 men and 32 women had an enucleation. The main indication was tumoral diseases, principally choroidal melanomas and ciliary melanomas (respectively, 26 and 8). More rarely the indication was orbital metastasis or eyelid carcinoma. The follow indications were traumatisms and neovascular glaucomas. The orbital implants used were mainly Allen implants, silicone implants and hydroxyapatite implants. The main complication was the expulsion of the implant, which occurred in about 20% of the cases, for the most part in the group of silicone and tunnel implants patient. These expulsions were found less with hydroyxapatite implants. For the hydroxyapatite implants we also noticed the some conjunctival erosion. The expulsion of the implant occurred most often before 2 years. CONCLUSION: The authors report on the survey of orbital implants used for 14 years. They noticed the high frequency of expulsions when they used tunnel or silicone implants and better results with hydroxyapatite implant.

Adolescent↗
PubMed2001

[Tarsomarginal graft. Indication and results in palpebral surgery].

A tarsomarginal graft is indicated in eyelid reconstructive surgery particularly after tumor resection. We reported the results of a retrospective study during the past 13 years with 58 grafts. We found a predominance of basal cell carcinomas localised in the lateral third portion of the lid (42%) and in the lower eyelid (76%). The mean size was 14mm for the tumor and 9.81mm for the graft. Grafts were used to cover a defect larger than 5mm. Complications were rare, and mainly involved suture looseness. The Hubner technique gave good results; repairing the eyelid without having to make a tarsorraphy and providing good cosmetic results. The graft must be covered by a skin flap.

Adolescent↗
PubMed2000

Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies?

BACKGROUND: Distinguishing well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine-needle aspiration (FNA) cytology. The endothelial cell marker CD34 is negative in normal hepatic sinusoids and stains vessels diffusely in HCC. This feature is useful in distinguishing benign from malignant hepatocytic lesions in histological specimens, although benign lesions may show focal positivity for CD34 confined to periportal and periseptal areas. In this study, we assess the role of CD34 in cell block and thin core biopsy material from benign and malignant hepatocellular lesions, and compare it with reticulin staining. METHODS: Cell blocks and thin core biopsies were assessed from 40 cases of HCC and 25 benign hepatocytic lesions. HCCs were scored for nuclear grade. Sections were stained for CD34 antigen and scored semi-quantitatively. Previously performed reticulin stains were reviewed. RESULTS: Thirty three of 40 HCCs (82.5%) showed diffuse positivity for CD34. The other seven cases showed either focal positivity (four cases), minimal positivity (two cases) or negative staining (one case). These results did not correlate with the nuclear grade of the tumor. Two of 25 benign cases (8%) showed diffuse positivity for CD34, 8 showed focal positivity, 11 showed minimal positivity, and 4 showed negative staining. All HCCs showed an abnormal reticulin pattern characterized by expanded trabeculae and islands, or sheets, with decreased or absent reticulin. All of the benign hepatocellular lesions showed a normal trabecular reticulin pattern. CONCLUSIONS: Diffusely positive CD34 staining is useful to support a diagnosis of well differentiated HCC, but in our study the reticulin stain distinguished more consistently between benign and malignant lesions.

Antigens, CD34↗
PubMed2000

The transport modifier RS1 is localized at the inner side of the plasma membrane and changes membrane capacitance.

Previously we cloned membrane associated (M(r) 62000-67000) polypeptides from pig (pRS1), rabbit (rbRS1) and man (hRS1) which modified transport activities that were expressed in Xenopus laevis oocytes by the Na(+)-D-glucose cotransporter SGLT1 and/or the organic cation transporter OCT2. These effects were dependent on the species of RS1 and on the target transporters. hRS1 and rbRS1 were shown to be intronless single copy genes which are expressed in various tissues and cell types. Earlier immunohistochemical data with a monoclonal IgM antibody suggested an extracellular membrane association of RS1. In the present paper antibodies against recombinant pRS1 were raised and the distribution and membrane localization of RS1 reevaluated. After subcellular fractionation of renal cortex RS1 was found associated with brush border membranes and an about 1:200 relation between RS1 and SGLT1 protein was estimated. Also after overexpression in X. laevis oocytes RS1 was associated with the plasma membrane, however, at variance to the kidney it was also observed in the cytosol. Labeling experiments with covalently binding lipid-permeable and lipid-impermeable biotin analogues showed that RS1 is localized at the inner side of the plasma membrane. Western blots with plasma membranes from Xenopus oocytes revealed that SGLT1 protein in the plasma membrane was reduced when hRS1 was coexpressed with human SGLT1 which leads to a reduction in V(max) of expressed glucose transport. Measurements of membrane capacitance and electron microscopic inspection showed that the expression of hRS1 leads to a reduction of the oocyte plasma membrane surface. The data suggest that RS1 is an intracellular regulatory protein that associates with the plasma membrane. Overexpression of RS1 may effect the incorporation and/or retrieval of transporters into the plasma membrane.

Animals↗
PubMed2000

Development of membrane extraction with a sorbent interface-micro gas chromatography system for field analysis.

The commercially available portable gas chromatographs have a rather limited scope of applications, typically allowing analysis of gaseous samples only, and having relatively poor sensitivity. Combination of those instruments with modern sampling/sample preparation techniques can remedy these problems. A Chrompack micro-GC system equipped with a thermal conductivity detector has been coupled to membrane extraction with a sorbent interface (MESI). The sorbent trap has replaced the GC injector. The design of the trap was also modified in order to enhance the preconcentration of analytes. The use of a thin flat sheet membrane reduces the response time, and decreases the memory effect of the system. Rapid separation times were achieved, and the sensitivity was significantly improved. MESI enables semi-continuous monitoring of both gaseous and aqueous samples, owing to the selectivity of the membrane material. The system does not use moving parts, therefore being reliable. The sensitivity of the micro-GC system was increased by a factor of more than 100 by the addition of the MESI system, even with a preconcentration time as short as 1 min. Chloroform, having a concentration lower than 1 ppb, was detected in tap water. A cup system was used to allow headspace sampling of volatile organic compounds from aqueous matrices, keeping the membrane away from interfering species that could be present in water, and improving the mass transfer. A linear calibration line was obtained, and the estimated limit of detection was 60 ppt. This represents a great improvement for the sensitivity of the micro-GC system.

Chromatography, Gas↗
PubMed2000

Cancer patient expectations of and communication with oncologists and oncology nurses: the experience of an integrated oncology and palliative care service.

The purpose of this study was to evaluate ambulatory cancer patients' knowledge of their diagnosis and stage, their expectations of medical and nursing staff, and issues related to communication with the professional staff. A structured interview was conducted with each of 103 consecutive cancer patients attending the Oncology Day Hospital of the Shaare Zedek Medical Center. There were 77 women and 26 men, and their median age was 56 (18-86) years. Their religious status was elicited: 48% described themselves as religious, 25% as traditional, and 27% as secular. According to their physicians, 41 were in remission, 11 had stable disease, 47 had progressive disease and in 4 the disease status was unknown. Patients tended to underestimate the status of their disease: among those with progressive disease, 36% stated that their disease was stable or in remission. Overwhelmingly, patients expected that their oncologists should be patient and skilled in diagnostic procedures (98%), tactful, considerate and therapeutically skilled (90-95%), and skilled in the management of pain and the psychosocial consequences of cancer (75-85%). When there is bad news to be transmitted, 92% of patients indicated that they would want disclosure, while 6% indicated that they would want the news withheld from them but passed on to their family members. Most patients were very satisfied with the clarity of the information they received about their disease (85%) and the sensitivity with which it was transmitted (90%). Although 88% of patients reported that they relied on their oncologist for therapeutic decision making, 45% indicated that they had sought a second opinion and 32% reported seeking the opinion of a rabbinical medical broker. Almost all, 97%, of patients indicated that they felt comfortable seeking advice from their oncologist, and the oncologist was the staff member most often sought out for both information (69%) and support (66%). The data indicate high patient expectations of nursing and medical oncology staff members' skills and behaviors. Despite expressing a high level of satisfaction, a substantial percentage of patients had an inaccurate understanding of their disease status.

Adult↗
PubMed2000

Helicobacter pylori: seroprevalence and colorectal cancer.

BACKGROUND: Previous studies have published controversial results regarding a connection between Helicobacter pylori infection and colorectal cancer. One possible mechanism is increased gastrin secretion in subjects infected with H. pylori, insofar as gastrin is known to be a trophic factor for the colonic mucosa. OBJECTIVES: To investigate a possible role of gastrin secretion in H. pylori infection associated with colorectal cancer, and determine whether H. pylori infection is a factor in this disease. METHODS: The serum gastrin levels and the presence of H. pylori IgG antibodies were measured in 51 colorectal cancer patients and 51 control subjects. The cancer patients were also tested for carcinoembryonic antigen and CA 19-9. RESULTS: H. pylori IgG antibodies were found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of the control subjects (P = 0.05). A significant correlation was found between CA 19-9 (r = 0.3432, n = 49, P = 0.01) and seropositive H. pylori IgG antibodies in the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99-5.95), but none between CEA and H. pylori IgG antibodies nor between the serum gastrin level and the presence of colorectal cancer. CONCLUSIONS: The results of this study indicate a significant association between seropositive H. pylori IgG antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation between the serum gastrin level and the presence of this cancer. H. pylori seropositivity is more prevalent in patients with colorectal cancer.

Adult↗
PubMed1999

Cytodiagnosis of well differentiated hepatocellular carcinoma: can indeterminate diagnoses be reduced?

BACKGROUND: Distinction of well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine-needle aspiration (FNA) cytology, sometimes leading to indeterminate reports. The aim of this study was to critically examine criteria that might allow definitive diagnosis in these cases. METHODS: FNA smears and cell blocks from 65 patients with primary hepatocellular lesions were reviewed. Seventy separate samples had been obtained. The initial reports in these samples were: HCC in 34, benign findings in 27, and indeterminate findings in 9. We defined architectural and cytological features seen in the malignant cases but not seen in the benign cases, including an assessment of reticulin in cell blocks. These criteria were then applied to the indeterminate cases. RESULTS: The most specific cytologic criteria of malignancy in well differentiated HCC were (i) numerous stripped atypical nuclei, (ii) macronucleoli, (iii) increased mitoses, and (iv) multinucleation. The most specific architectural criteria in smears were (i) widened trabeculae, (ii) well defined capillaries traversing tissue fragments, and (iii) solid islands of hepatocytes rimmed by endothelial cells. The most valuable architectural criteria in cell blocks were (i) trabeculae greater than two cells thick and (ii) reduced or absent reticulin framework. Using the above criteria a retrospective diagnosis of HCC was possible in eight of the nine indeterminate cases, all but one of which have subsequently been confirmed as malignant. CONCLUSIONS: Close attention to architectural features in both smears and cell blocks should allow most well differentiated HCCs to be diagnosed by FNA cytology. A reticulin stain should be part of the routine assessment of cell blocks. Cancer (Cancer Cytopathol)

Adult↗
PubMed1999

Preoperative angiography and embolization of large pelvic tumors.

BACKGROUND AND OBJECTIVES: Pelvic tumors are often large and difficult to excise with appropriate surgical margins due to their size, proximity to neurovascular structures, and major intraoperative bleeding. The purpose of this study is to evaluate the yield of preoperative angiography and embolization so as to facilitate achievement of good surgical results. METHODS: Eighteen patients who suffered from large pelvic tumors (average size, 10.7 cm x 8.3 cm x 3.7 cm), 15 primary and 3 metastatic, underwent surgery at our institution between 1990 and 1995, after preoperative angiography and embolization of the tumors. RESULTS: The efficacy of the procedure was high. In all but one patient, the grade of vascularity of the tumor was reduced by at least two levels (based on our new tumor vascularity scale. In most patients, appropriate surgical margins were achieved. The average perioperative blood loss was only 750 cc. Procedure-associated complications were negligible. CONCLUSIONS: The results of this study call for the use of angiography and embolization in the management of patients with large pelvic tumors.

Angiography↗
PubMed1999

Reconstitution of GTPgammaS-induced NADPH oxidase activity in streptolysin-O-permeabilized neutrophils by specific cytosol fractions.

GTPgammaS activates the NADPH oxidase and this activity declines rapidly with time after preexposure to streptolysin O. This was not due to loss of p47(phox), p67(phox), or Rac. To identify the component(s) leaking out of the permeabilized cell responsible for loss of activity, a GTPgammaS-dependent reconstitution assay was established. Neutrophil cytosol was subjected to chromatographic fractionation steps for purification of the minimum fraction required to restore activity. The reconstitution of the GTPgammaS-stimulated activity was dependent on ATP. The inhibitors staurosporine and calphostin C greatly reduced the activity in the reconstitution assay, implicating the involvement of a protein kinase C (PKC) pathway. PKC isoforms beta and delta were eliminated as the active factors in the most pure reconstitution fraction. With this novel cell-based reconstitution assay, we have identified the requirement for a protein kinase, or its substrate, for the restoration of GTPgammaS activation of the NADPH oxidase.

Bacterial Proteins↗