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Biomedical subjects

G Weinstein

Publications and source records attributed to G Weinstein.

At least 19 recordsLinked to original sources
PubMed2004

Molecular cytogenetic parameters in fibroblasts from patients and carriers of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive syndrome. Laboratory investigations have failed to detect any consistent anomaly in cells from XP heterozygotic subjects, although examples of behavior intermediate between normal and XP cells have been reported. To estimate random aneuploidy we applied fluorescence in situ hybridization (FISH) with alpha-satellite probes for chromosomes 8 and 9 and replication pattern for TP53 (p53), ERBB2 (HER-2/neu), and MYCN (N-MYC) loci and for the imprinted SNRPN locus. A significantly higher rate of aneuploidy rate was observed in XP patients and carriers than in controls. The asynchrony pattern was significantly higher in XP carriers and patients with all three coding loci analyzed and significantly lower in XP patients and carriers with the imprinted locus SNRPN than in the control group. Molecular cytogenetic parameters such as random aneuploidy and replication pattern, which are known to reflect chromosomal instability, may be part of the tumorigenesis process. In XP patients and carriers, this genetic instability may represent a potential for developing malignancies.

Aneuploidy↗
PubMed2004

Molecular cytogenetic parameters in fibroblasts of ataxia telangiectasia carrier.

Ataxia telangiectasia (AT) is a pleiotropic and rare (1:40,000 to 1:100,000) recessive disease. Laboratory investigations have failed to detect any consistent anomaly in cells from AT heterozygotes. To estimate random aneuploidy, we applied a fluorescence in situ hybridization technique with alpha-satellite probes for chromosomes 8 and 9 and replication pattern for RB-1, HER-2/neu, and the imprinted SNRPN loci on primary AT carrier fibroblasts. Higher random aneuploidy was not found in the carrier fibroblasts compared to control amniocytic cells. The asynchrony pattern was higher in the AT carrier cells with the RB-1 locus (P=0.057) and significantly higher with the HER-2/neu locus (P < 0.001) compared to control cells. As for the imprinted locus SNRPN, there was a significantly lower asynchrony rate in the AT carriers (P < 10(-5)) compared to the control group. Molecular cytogenetic parameters of random aneuploidy and replication pattern may reflect predisposition for the development of cancer. It is possible that in some AT carriers the genetic instability phenomena associated with the abnormal replication pattern may represent their potential for developing malignancies.

Aneuploidy↗
PubMed2001

Intrinsic connectivity of the rat subiculum: I. Dendritic morphology and patterns of axonal arborization by pyramidal neurons.

The dendritic and axonal morphology of rat subicular neurons was studied in single cells labeled with Neurobiotin. Electrophysiological classification of cells as intrinsic burst firing or regular spiking neurons was correlated with morphologic patterns and cell locations. Every cell had dendritic branches that reached the outer molecular layer, with most cells having branches that reached the hippocampal fissure. All but two pyramidal cells had axon collaterals that entered the deep white matter (alveus). Branching patterns of apical dendrites varied as a function of the cell's soma location along the fissure-alveus axis of the cell layer. The first major dendritic branch point for most cells occurred at the superficial edge of the cell layer giving deep cells long primary apical dendrites and superficial cells short or absent primary apical dendrites. In contrast, basal dendritic arbors were similar across cells regardless of cell position. Apical and basal dendrites of all cells had numerous spines. Superficial and deep cells also differed in axonal collateralization. Deep cells (mostly intrinsically bursting [IB] class) had one or more ascending axon collaterals that typically remained within the region circumscribed by their apical dendrites. Superficial cells (mostly regular spiking [RS] class) tended to have axon collaterals that reached longer distances in the cell layer. Numerous varicosities and axonal extensions were present on axon collaterals in the cell layer and in the apical dendritic region, suggesting intrinsic connectivity. Axonal varicosities and extensions were found on axons that entered presubiculum, entorhinal cortex or CA1, supporting the notion that these were projection cells. Local collaterals were distinctly thinner than collaterals that would leave the subiculum, suggesting little or no myelin on local collaterals and some myelin on efferent fibers. We conclude that both IB and RS classes of subicular principal cells make synaptic contacts in and apical to the cell layer. Based on the patterns of axonal arborization, we suggest that subiculum has at least a crude columnar and laminar architecture, with ascending collaterals of deep cells forming columns and broader axonal arbors of superficial cells serving to distribute activity across multiple columns.

Animals↗
PubMed2001

Fetal cells in the uterine cervix: a source for early non-invasive prenatal diagnosis.

Various non-invasive techniques for prenatal diagnosis have been under investigation. We evaluated the success of fetal sexing using a non-invasive technique for obtaining fetal cells, uterine cervix brushing, in combination with FISH. Thirty pregnant women who completed between 6 and 10 weeks of gestation and who were scheduled to undergo pregnancy termination were included in the study. A Pap smear cytobrush was inserted through the external os to a maximum depth of 2 cm and removed while rotating it a full turn. The material that was caught on the brush was spread on four microscope slides. Two-color FISH was used for fetal sexing. Following pregnancy termination, a placental sample was used for full karyotyping. In 29/30 cases FISH diagnosis was confirmed by chromosomal analysis. The only male case in which a Y chromosome was not seen was from a pregnancy of 6 weeks 6 days gestational age. One case was mosaic of 46,XY/47,XXY (25%). In most cases (7/13) the Y chromosome was already identified in the first analyzed slide. With the use of a cytobrush fetal cells can be easily obtained for the purpose of prenatal diagnosis of chromosomal disorders.

Cervix Uteri↗
PubMed2000

Detection of hypoxia in human squamous cell carcinoma by EF5 binding.

Localization and quantitation of 2-nitroimidazole drug binding in low pO2 tumors is a technique that can allow the assessment of hypoxia as a predictive assay. EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] is such a drug, and it has been shown to be predictive of radiation response in rodent tumors. Using fluorescence immunohistochemical techniques, we provide data on the presence, distribution, and levels of EF5 binding as a surrogate for hypoxia in human head and neck and uterine cervix squamous cell cancers (SCCs). Six patients with SCC were studied. Four patients had head and neck tumors, and two had uterine cervix cancers. The incubation of fresh tissue cubes in EF3 under hypoxic conditions ("reference binding") demonstrated that all tumors were capable of binding drug, and that this binding varied by a factor of 2.9-fold (174.5-516.1) on an absolute fluorescence scale. In the five patients treated at the lowest drug doses (9 mg/kg), in situ binding was quantitatable. For all six patients, the maximum rate of in situ binding varied by a factor of 6.7 between the lowest and highest binding tumor (24.8-160.3) on an absolute fluorescence scale. In tumors with high binding regions, intratumoral heterogeneity was large, extending from minimal fluorescence (<1%) up to 88.6% of reference binding. In tumors with minimal binding, there was little intratumoral heterogeneity. These studies demonstrate substantial heterogeneity of in situ binding between and within individual squamous cell tumors.

Adult↗
PubMed2000

Vertical partial laryngectomy versus supracricoid partial laryngectomy for selected carcinomas of the true vocal cord classified as T2N0.

From an inception cohort of 204 patients with squamous cell carcinoma of the true vocal cord classified as T2N0 and a minimum of 3 years of follow-up, the authors compare the oncological and functional outcomes following vertical partial laryngectomy (group 1; 85 patients) and supracricoid partial laryngectomy (group 2; 119 patients). The 10-year actuarial survival estimate was 46.2% for group 1 and 66.4% for group 2. Survival was statistically more likely to be reduced (p = .019) in group 1 than in group 2. The 10-year actuarial local control estimate was 69.3% for group 1 and 94.6% for group 2. Local recurrence was statistically more likely to occur (p < .0001) in group 1 than in group 2. Salvage treatment resulted in an overall 94.1% local control rate and a 78.1% laryngeal preservation rate for group 1 and an overall 99.2% local control rate and a 94.9% laryngeal preservation rate for group 2. The 10-year actuarial nodal control estimate was 81.7% for group 1 and 93.7% for group 2. Nodal recurrence was statistically more likely to occur (p = .028) in group 1 than in group 2. The 10-year actuarial estimate for patients without distant metastasis was 84.6% for group 1 and 95.1% for group 2. Distant metastasis was statistically more likely to occur (p = .05) in group 1 than in group 2. The hospital mortality rate was 1.2% for group 1 and 0.8% for group 2. The incidence of permanent gastrostomy was 0% for group 1 and 2.4% for group 2. The incidence of permanent tracheostomy was 1.2% for group 1 and 2.4% for group 2. The incidence of completion laryngectomy due to functional problems was 1.2% for group 1 and 0.8% for group 2.

Actuarial Analysis↗
PubMed1998

Neo-adjuvant chemotherapy and supracricoid partial laryngectomy with cricohyoidopexy for advanced endolaryngeal carcinoma classified as T3-T4: 5-year oncologic results.

BACKGROUND: Historically, total laryngectomy with voice-prosthesis insertion and near-total laryngectomy were the surgical options advocated for advanced supraglottic and transglottic tumors classified as T3-T4. METHODS: The present retrospective study reviewed our experience with neo-adjuvant chemotherapy and supracricoid partial laryngectomy with cricohyoidopexy (SCPL-CHP) in a series of 60 patients with an isolated, untreated, advanced supraglottic/transglottic invasive squamous cell carcinoma classified as T3-T4. RESULTS: The Kaplan-Meier 5-year actuarial survival, local failure, nodal failure, and distant metastasis estimates were 72.7%, 8.3%, 9.2%, and 9.8%, respectively. Survival was significantly reduced in patients with nodal failure (p = .001) and distant metastasis (p = .007). Overall, a 91.7% laryngeal preservation rate and a 98.3% local control rate were achieved. CONCLUSION: Our report was a retrospective analysis and did not present a control group exclusively managed with SCPL-CHP. Therefore, we were unable to demonstrate that the use of neo-adjuvant chemotherapy prior to SCPL-CHP allowed for an increase in local control, laryngeal preservation, and survival. However, the use of neo-adjuvant chemotherapy allowed for remobilization of a fixed arytenoid cartilage in 10 patients who thus became amenable to SCPL-CHP. The key role of neo-adjuvant chemotherapy in this series was as a prognostic indicator for suitability for SCPL-CHP in the case of supraglottic-transglottic tumor with arytenoid cartilage fixation. Our data also supported the notion that SCPL-CHP is a valid alternative to total laryngectomy with voice prosthesis insertion and near-total laryngectomy in selected patients with a previously untreated supraglottic/transglottic invasive squamous cell carcinoma classified as T3-T4. Furthermore, the successful use (in terms of surgical outcome, laryngeal preservation, and survival) of SCPL-CHP after neo-adjuvant chemotherapy suggested that laryngeal organ-preservation strategies, in advanced endolaryngeal transglottic and/or supraglottic invasive squamous cell carcinoma, should not be limited to the use of laryngeal radiotherapy after neo-adjuvant chemotherapy.

Adult↗
PubMed1998

Cyclosporine consensus conference: with emphasis on the treatment of psoriasis.

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporine's use in rotational therapy.

Contraindications↗
PubMed1998

Complications and functional outcome after supracricoid partial laryngectomy with cricohyoidoepiglottopexy.

We present a review of the postoperative course, complications, and functional outcome of 190 patients consecutively treated with supracricoid partial laryngectomy with cricohyoidoepiglottopexy. The average times until removal of the tracheostomy and nasogastric feeding tubes were 9 and 16 days, respectively. The postoperative mortality rate was 1%. Major complications included pneumonia from aspiration, cervical wound infection, symptomatic laryngocele, ruptured pexis, laryngeal chondroradionecrosis, and laryngeal stenosis in 8.5%, 4.2%, 3.1%, 1%, 0.5%, and 0.5% of the patients, respectively. Completion total laryngectomy, permanent gastrostomy, and permanent tracheostomy were requested in 0.5% of the patients. Normal swallowing without gastrostomy and respiration without tracheostomy was achieved by the first postoperative year in 98.4% (187/190) of the patients. This article presents a univariate analysis of the potential correlation between various variables and the duration of tracheostomy and the length of time the nasogastric feeding tubes were inserted, the mortality incidence and causes, the incidence and type of the various complications, and the duration of hospitalization. Comparison of our data with the reported functional results after vertical partial laryngectomy suggested that supracricoid partial laryngectomy with cricohyoidoepiglottopexy does not result in an increased rate of postoperative complications.

Deglutition↗
PubMed1998

Supracricoid partial laryngectomies in the elderly: mortality, complications, and functional outcome.

A review of the postoperative course, complications, and functional outcome of 69 elderly patients (older than 65 years of age) consecutively managed with a supracricoid partial laryngectomy between 1977 and 1993 is presented. The tumors were glottic and supraglottic in origin in 53 and 16 patients, respectively. A cricohyoidoepiglottopexy, a tracheo-cricohyoidoepiglottopexy, and a cricohyoidopexy were performed in 48, five, and 16 patients, respectively. Immediate laryngeal, cervical, and medical complications were noted in 5.8%, 10.2%, and 10.2% of patients, respectively. Supracricoid partial laryngectomies never resulted in perioperative or postoperative death. The 5-year actuarial survival and local control estimates were 68%, and 93.9%, respectively. Late surgical complications included laryngocele, laryngeal stenosis, and pneumonia from aspiration-related death in 4.3%, 4.3%, and 1.4% of patients, respectively. Completion total laryngectomy, permanent gastrostomy, and permanent tracheostomy were requested in 1.4%, 1.4%, and 2.91% of patients, respectively. Overall a 92.8% laryngeal preservation rate was achieved. Univariate analysis of the potential correlation of different factors with the mortality incidence and causes, the incidence and type of the various complications, and the incidence for postoperative aspiration is presented.

Actuarial Analysis↗
PubMed1998

Local failure after supracricoid partial laryngectomy: symptoms, management, and outcome.

The medical files of 15 patients with local recurrence after supracricoid partial laryngectomy consecutively managed at Laënnec Hospital were reviewed. The clinical symptoms and the laryngeal computed tomography appearance of local recurrence, as well as the salvage treatment performed, are presented. The main presenting symptom was dyspnea. None of the local recurrences was considered to be unresectable. One patient refused any form of salvage treatment. Radiation therapy and salvage total laryngectomy were the options retained for local salvage. A minimum 5-year follow-up was always achieved. In patients who underwent salvage total laryngectomy, perioperative or postoperative death and postoperative pharyngocutaneous fistula were not encountered. The 5-year survival was 33.3%. The local control rate was 66.6%. The percentage of patients who experienced nodal recurrence was 26.6%, and the distant metastasis estimate was 53.3%. The cause of death was distant metastasis in eight patients, local recurrence in two, and intercurrent disease in one. Peristomal recurrence was not encountered. Overall, 80% local control and 6.6% laryngeal preservation rates were achieved.

Adult↗
PubMed1997

Combined surgery and postoperative radiotherapy for carcinoma of the base of radiotherapy for carcinoma of the base of tongue: analysis of treatment outcome and prognostic value of margin status.

BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.

Actuarial Analysis↗
PubMed1997

Head and neck manifestations of plasma cell neoplasms.

Multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma are plasma cell neoplasms. They represent distinct manifestations of a disease continuum, whereby the clinical findings are critical to diagnosis. Plasma cell neoplasms are histologically similar, and distinguishing one from the other has significant implications for treatment and survival. Plasma cell neoplasms are relatively unusual malignancies of the head and neck region. We present a case series of plasma cell neoplasms involving the skull base, paranasal sinus, larynx, and mandible as an introduction to a complete review of the literature on plasma cell neoplasms of the head and neck area.

Adult↗
PubMed1997

Functional outcome and prognosis factors after supracricoid partial laryngectomy with cricohyoidopexy.

A retrospective analysis of the medical records and operative files of 124 patients who consecutively underwent supracricoid partial laryngectomy with cricohyoidopexy (SCPL-CHP) was undertaken. The objective of this study was to analyze the postoperative course and functional results of SCPL-CHP. The mean duration of follow-up was 7 years (range 1 to 20 years). The postoperative mortality was 1.6%. The average times until tracheostomy and nasogastric feeding tube removal were 8 and 22 days, respectively. All patients but 1 were decannulated. The rate of pneumonia from aspiration was 11.5%. Completion total laryngectomy and permanent gastrostomy were required in 2.5% and 2.5% of patients, respectively. Overall normal swallowing without permanent gastrostomy and respiration without tracheostomy were achieved by the first postoperative year in 91% and 99.1% of patients, respectively. Univariate analysis of the potential correlation between various variables and the duration of the tracheostomy and nasogastric feeding tube, the incidence and causes of mortality, the incidence and type of the various complications, the recovery of swallowing, and the length of hospitalization is presented. The report also discusses the management and follow-up care.

Adult↗