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Biomedical subjects

L Ginsberg

Publications and source records attributed to L Ginsberg.

At least 19 recordsLinked to original sources
PubMed2006

Effective treatment of an elderly patient with Gaucher's disease and Parkinsonism: a case report of 24 months' oral substrate reduction therapy with miglustat.

We report here the results of 24 months' treatment with oral miglustat of a patient with mild-to-moderate Gaucher's disease (GD) and Parkinsonism. The patient's progressive Parkinsonian tremor, in addition to restricted vascular access, necessitated switching treatment for GD from intravenously infused enzyme replacement therapy (ERT) that had been administered for the previous 7 years. With control of haematological parameters and markers of GD activity improved or maintained and no notable adverse effects, miglustat treatment proved an effective and well-tolerated therapeutic alternative to ERT. Oral miglustat should be considered for the treatment of patients with type I GD and concurrent movement disorders who are unsuitable for ERT.

1-Deoxynojirimycin↗
PubMed2005

Natural history of the cerebrovascular complications of Fabry disease.

UNLABELLED: Fabry disease is a rare, X-linked lysosomal storage disease caused by an inborn deficiency of alpha-galactosidase A, which results in progressive accumulation of globotriaosylceramide in a range of cells and tissues. Neurological symptoms of Fabry disease, including peripheral neuropathy and cerebrovascular events, are among the most significant clinical aspects. In this paper we present the natural history and mechanisms involved in the cerebrovascular complications of Fabry disease using data reported in FOS-- the Fabry Outcome Survey--and other registries and clinical studies. We discuss ways in which these manifestations can be modified by intervention, including both general measures for cerebrovascular disease and enzyme replacement therapy. CONCLUSION: Data from FOS have provided important insights into the natural history of the cerebrovascular complications of Fabry disease. Furthermore, the database has demonstrated that significant renal or cardiac disease often co-exists with cerebrovascular disease, and may predispose patients with Fabry disease to neurological disability and stroke.

Adult↗
PubMed2004

Exophytic ependymomas of the spinal cord.

Intramedullary ependymomas of the spinal cord with exophytic components are rare outside the filum or conus region. Two cases of combined intradural intramedullary and extramedullary ependymomas of the spinal cord are presented. At operation, the tumours proved to be primarily intramedullary but had a contiguous exophytic component that extruded either through a defect in the ventral pia to encase the anterior spinal artery in one patient, or through the dorsal root entry zone in the second patient. When removing intramedullary spinal tumours with an exophytic component, separate removal of the intramedullary and extramedullary components is recommended, rather than en bloc resection, to prevent possible injury to the vascular supply of the spinal cord.

Adult↗
PubMed2002

Peripheral nerve granuloma in a patient with tuberculosis.

The cause of peripheral neuropathy associated with tuberculosis is controversial. Possibilities include an immune mediated neuropathy, direct invasion of nerves, vasculitic neuropathy, compressive neuropathy, a meningitic reaction, and the toxic effects of antituberculous chemotherapy. This report describes the unusual finding of granulomas in the peripheral nerve of a patient with tuberculosis. The pathological findings were of a delayed hypersensitivity reaction, but with no more specific indications of the mechanism of the neuropathy.

Adult↗
PubMed2001

Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: novel bioadjuvant phase II trial.

PURPOSE: Retinoids and interferons (IFNs) have single-agent and synergistic combined effects in modulating cell proliferation, differentiation, and apoptosis in vitro and clinical activity in vivo in the head and neck and other sites. Alpha-tocopherol has chemopreventive activity in the head and neck and may decrease 13-cis-retinoic acid (13-cRA) toxicity. We designed the present phase II adjuvant trial to prevent recurrence or second primary tumors (SPTs) using 13-cRA, IFN-alpha, and alpha-tocopherol in locally advanced-stage head and neck cancer. PATIENTS AND METHODS: After definitive local treatment with surgery, radiotherapy, or both, patients with locally advanced SCCHN were treated with 13-cRA (50 mg/m(2)/d, orally, daily), IFN-alpha (3 x 10(6) IU/m(2), subcutaneous injection, three times a week), and alpha-tocopherol (1,200 IU/d, orally, daily) for 12 months, with a dose modification. Screening for recurrence or SPTs was performed every 3 months. RESULTS: Tumors of 11 (24%) of the 45 treated patients were stage III, and 34 (76%) were stage IV. Thirty-eight (86%) of 44 patients completed the full 12-month treatment (doses modified as needed). Toxicity generally was consistent with previous IFN and 13-cRA reports and included mild to moderate mucocutaneous and flu-like symptoms; occasional significant fatigue (grade 3 in 7% of patients), mild to moderate hypertriglyceridemia in 30% of patients who continued treatment along with antilipid therapy, and mild hematologic side effects. Six patients did not complete the planned treatment because of intolerable toxicity or social problems. At a median 24-months of follow-up, our clinical end point rates were 9% for local/regional recurrence (four patients), 5% for local/regional recurrence and distant metastases (two patients), and 2% for SPT (one patient), which was acute promyelocytic leukemia (ie, not of the upper aerodigestive tract). Median 1- and 2-year rates of overall survival were 98% and 91%, respectively, and of disease-free survival were 91% and 84%, respectively. CONCLUSION: The novel biologic agent combination of IFN-alpha, 13-cRA, and alpha-tocopherol was generally well tolerated and promising as adjuvant therapy for locally advanced squamous cell carcinoma of the head and neck. We are currently conducting a phase III randomized study of this combination (v no treatment) to confirm these phase II study results.

Adult↗
PubMed2001

Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma.

BACKGROUND: In the current study the authors assessed the antitumor activity (including response rate, duration of response, and survival) and toxicity profile (including anorexia, fatigue, emesis, and peripheral neuropathy) of a combination of paclitaxel, ifosfamide, and carboplatin (TIC) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The trial hypothesis was that the TIC therapeutic index would be as high as that of paclitaxel, ifosfamide, and cisplatin (TIP) in this setting, but with less toxicity. METHODS: Patients with recurrent or metastatic SCCHN were treated with 175 mg/m(2) of paclitaxel as a 3-hour infusion on Day 1, 1000 mg/m(2) of ifosfamide as a 2-hour infusion on Days 1-3, 600 mg/m(2) of mesna on Days 1-3, and carboplatin (area under the concentration-time curve of 6) as a 30-minute infusion on Day 1; the regimen was repeated every 3-4 weeks. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine before paclitaxel infusion. Prophylactic hematopoietic growth factors were not given. RESULTS: Among 56 patients entered onto the study, 55 patients were analyzed for survival rates (locoregional recurrence alone in 56% of patients and distant metastasis with or without locoregional recurrence in 44% of patients). Fifty-four patients were evaluable for tumor response and toxicity. A total of 32 patients (59%) had disease that responded to treatment; the complete response rate was 17% (9 of 54 patients). The median duration of the responses was 3.7 months (95% confidence interval [95% CI], 3.4-7.8 months) and that of complete responses was 9.7 months (95% CI, 7.4 months to date of last follow-up). The median duration of follow-up care in all patients was 13.5 months. The median survival time for all patients was 9.1 months (95% CI, 7.9-12.2 months). The regimen was well tolerated. Neutropenic fever developed in 30% of the patients; 1 patient died of neutropenia and sepsis. Other toxic effects included Grade 2-3 anorexia in 13% of patients, Grade 2-3 weight loss in 11% of patients, Grade 2-3 fatigue in 27% of patients, Grade 2-3 nausea/emesis in 13% of patients, and Grade 2-3 peripheral neuropathy in 9% of patients (toxicity grading based on the National Cancer Institute's Common Toxicity Criteria). Red blood cell and platelet transfusions were required in 13% and 7% of patients, respectively. CONCLUSIONS: The TIC regimen had high antitumor activity in patients with recurrent or metastatic SCCHN, with a 59% major response rate (17% complete response rate with relatively durable complete responses). Neutropenic fever developed in 30% of the patients, the incidence of which might have been decreased by prophylactic antibiotics or hematopoietic growth factor support. Other toxic effects included significantly lower rates and less severe instances of anorexia, emesis, fatigue, and peripheral neuropathy than those reported with the previously studied TIP regimen. The TIC regimen currently is being studied as an induction chemotherapy regimen in previously untreated patients with locally advanced SCCHN. The activity of TIC (a novel paclitaxel and ifosfamide-based regimen) in patients with recurrent or metastatic SCCHN should be confirmed in a Phase III randomized trial.

Adult↗
PubMed2001

Orbital mass secondary to precursor T-cell acute lymphoblastic leukemia: a rare presentation.

We describe a 40-year-old woman with a history of precursor T-cell acute lymphoblastic leukemia who developed an orbital mass associated with diffuse infiltration of the paranasal sinuses. The clinical and radiologic findings suggested an orbital abscess. Examination of orbital and ethmoid sinus biopsy specimens revealed relapse of precursor T-cell acute lymphoblastic leukemia. Although orbital involvement by granulocytic sarcoma (also known as extramedullary myeloid cell tumor and chloroma) with or without concurrent acute myeloid leukemia is well described in the literature, similar presence of acute lymphoblastic leukemia of either precursor T-cell or B-cell lineage is rare.

Adult↗
PubMed2001

The role of neck dissection after chemoradiotherapy for oropharyngeal cancer with advanced nodal disease.

OBJECTIVE: To analyze and compare the effectiveness of sequential platinum-based chemotherapy and radiotherapy with and without selective neck dissection in patients with N2a and greater stage node-positive squamous cell carcinoma of the oropharynx. DESIGN: Nonrandomized controlled trial. SETTING: Tertiary referral center. PATIENTS: Sixty-six patients with squamous cell carcinoma of the oropharynx staged N2a or greater. INTERVENTIONS: Platinum-based induction chemotherapy followed by definitive radiation therapy; and selective neck dissections 6 to 10 weeks following the completion of radiation therapy in patients with radiographic evidence suggesting residual neck disease. MAIN OUTCOME MEASURES: Locoregional recurrence and disease-free survival. RESULTS: Of 66 patients, 24 (36%) had complete responses in the primary local tumor (oropharynx) and regional disease (neck nodes), as assessed clinically and radiographically. These patients had lower rates of locoregional recurrence than did patients showing no or partial responses, but the differences were not significant (P>.05). Of 18 patients undergoing neck dissection, 10 (56%) had pathological evidence of residual tumor. Patients showing a complete response of regional and neck disease had significantly improved disease-specific and overall survival (P = .01 for both) compared with patients showing no or partial responses of their neck disease. Patients with no or partial responses who underwent neck dissections had significantly improved overall survival compared with similar patients who did not undergo neck dissections (P = .002). CONCLUSIONS: Even in patients with bulky nodal disease, a complete response in the neck to sequential chemotherapy and radiotherapy may indicate that neck surgery is not necessary for good locoregional control and improved disease-free survival. Neck dissection is recommended for patients with no or partial radiographic responses.

Adult↗
PubMed2001

Regulation of proximal tubule sodium/hydrogen antiporter with chronic volume contraction.

We developed a model of volume contraction in rabbits by using a furosemide/low-salt diet to follow changes, if any, in proximal tubule Na+/H+ exchanger 3 (NHE3) mRNA and brush-border protein. The rabbits' plasma renin, aldosterone, and urine sodium content confirmed the volume-contracted state. RNase protection assays demonstrated increases in treated-animal NHE3 mRNA as a percentage of control with 172 +/- 23, 154 +/- 15, 153 +/- 14, and 141 +/- 7 (SE) % (P < 0.05) at 1, 5, 10, and 31 days, respectively. Western analysis of brush-border membrane with NHE3 antibody revealed increased immunoreactivity in treated animals as a percentage of control with 120 +/- 30, 190 +/- 59, 307 +/- 72, and 427 +/- 41% (P < 0.05) at 1, 5, 10, and 31 days, respectively. There was no significant difference in serum potassium, bicarbonate, and cortisol in control vs. experimental animals. These data suggest that there is chronic upregulation of NHE3 in the volume-contracted state.

Animals↗
PubMed2000

Quinagolide in the management of prolactinoma.

OBJECTIVE: This study reports a six year experience with quinagolide (CV205-502) in the treatment of 40 patients with hyperprolactinemia or prolactinoma. PATIENTS AND MEASUREMENTS: Forty patients with hyperprolactinemia were treated with quinagolide (CV 205-502, Norprolac) for 2-72 months (mean 31.6 months). The patient's ages ranged from 12 to 53 years and 90% were female. Seventeen had no radiologic evidence of tumor; 11 had microadenomas; and 12 had macroadenomas. RESULTS: All patients had a reduction of the serum prolactin following quinagolide therapy with normalization in 82% with no tumor, 73% with microadenomas, and 67% with macroadenomas. Fifty-five percent of microadenoma and 75% of macroadenoma patients had a decrease in tumor size when assessed by a blinded reviewer. Ten of 38 female patients became pregnant while taking quinagolide. The dosage of quinagolide ranged from 75 to 400 [mgr]g/day with a median dose of 100[mgr]g/day. A comparison of side effects in a subgroup of 35 patients who had taken bromocriptine prior to quinagolide administration showed a greater than 75% reduction in nausea, vomiting, dizziness, and drowsiness during quinagolide administration. CONCLUSIONS: We conclude that quinagolide is a safe and effective long-term alternative to bromocriptine therapy, particularly in those individuals with bromocriptine intolerance.

Adolescent↗
PubMed2000

Squamous cell carcinoma with perineural invasion presenting as a Tolosa-Hunt-like syndrome: a potential pitfall in diagnosis.

PURPOSE: To describe a case of perineural invasion resulting from squamous cell carcinoma of forehead. METHODS: Case report. RESULTS: Perineural invasion resulting from squamous cell carcinoma of the periocular skin can present as a Tolosa-Hunt-like syndrome with lack of radiologic findings on magnetic resonance imaging (MRI) in its early stages. CONCLUSION: A high level of suspicion for perineural invasion is required when assessing multiple cranial nerve palsies in patients with a history of cutaneous malignancy, despite negative sequential MRI. Perineural invasion must be ruled out by a biopsy of the involved nerves, whenever possible, before empiric therapy with systemic steroids is contemplated.

Biopsy↗
PubMed1998

Membrane instability, plasmalogen content, and Alzheimer's disease.

The normal stability of the cell membrane bilayer depends on its lipid composition being appropriate to the ambient (physiological) temperature, Tp. Membrane lipid composition may be altered by disease such that the bilayer is only stable at a new critical temperature, T*, which may differ from Tp. In Alzheimer's disease (AD) temporal cortex, a defect of lipid composition has previously been identified, namely, a decrease in the ratio of plasmalogen to nonplasmalogen ethanolamine glycerophospholipids. Furthermore, for AD temporal cortex neural membranes, T* << Tp, a finding confirmed in the present study in a larger series than previously, using a new method for obtaining T*. This inequality between T* and Tp has been proposed as a putative contributory pathogenetic mechanism leading to membrane destabilisation in AD brain. The plasmalogen deficiency could account for the change in T* in AD, as shown by experiments where T* was measured for artificial lipid mixtures simulating brain membranes with varying plasmalogen/nonplasmalogen ratios. The critical temperature was found to be very sensitive to small alterations in plasmalogen content.

Aged↗
PubMed1998

Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma.

PURPOSE: To assess the activity and toxicity profile of combined taxol (paclitaxel), ifosfamide, and platinum (cisplatin) (TIP) in patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck. PATIENTS AND METHODS: Recurrent or metastatic head and neck SCC patients received paclitaxel 175 mg/m2 in a 3-hour infusion on day 1; ifosfamide 1,000 mg/m2 in a 2-hour infusion on days 1 through 3; mesna 600 mg/m2 on days 1 through 3; and cisplatin 60 mg/m2 on day 1, repeated every 3 to 4 weeks. All were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic hematopoietic growth factors were not permitted. RESULTS: Fifty-two patients were assessable for response and toxicity; 53 for survival (local-regional recurrence alone in 57% and distant metastasis with or without local-regional recurrence in 43%). Overall response rate was 58% (30 of 52) of patients; complete response rate was 17% (nine of 52) of patients, with six complete responses that continued for a median 15.7+ months. Median follow-up of all patients was 17.7 months. Median survival was 8.8 months (95% confidence interval [CI] 8.1 to 17.5 months). Toxicity was relatively well tolerated and caused no deaths. The most frequent moderate-to-severe toxicity (90% of patients) was transient grades 3 to 4 neutropenia; neutropenic fever occurred in 27%. Grade 3 peripheral neuropathy occurred in three patients, none had grade 4. Grade 3 mucositis occurred in only one patient, none had grade 4. CONCLUSION: TIP had major activity in this setting, with a 58% objective response rate, 17% complete response rate, durable complete responses (six of nine persisting), and relatively well-tolerated toxicity, with no toxic deaths. The activity of TIP, a novel taxol-cisplatin-based regimen, in recurrent or metastatic head and neck SCC should be confirmed in a phase III trial.

Adult↗
PubMed1998

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

Adenoviridae↗
PubMed1997

Probing the critical unilamellar state of membranes.

Aqueous dispersions of membrane phospholipids comprised of multilamellar vesicles (MLVs) will spontaneously transform to a stable unilamellar structure equivalent to the membrane bilayer, but only at a critical temperature T*. Since much of the evidence for this transformation derives from equilibrium thermodynamic studies, a description of the molecular and topological events occurring as the critical unilamellar state assembles has not previously been possible. Here we report experiments that provide evidence of a spontaneous topological change from MLVs towards unilamellar vesicles (ULVs) at T*. By applying a shearing stress to vesicle suspensions we have observed a decrease of approximately 25% in the force required to cause bilayers to leak; this decrease is confined to temperatures near T*. The T* values observed agree with those previously obtained by equilibrium methods. Using the method with total lipid extracts from normal biological membranes confirms that T* equals the physiological temperature of the original membranes.

Cell Membrane↗
PubMed1997

Age-related changes in cognitive ERPs of attenuation.

This investigation explored developmental changes in passive and effortful components of ERPs associated with a visual attention task in children, adolescents, and adults. The task was a 'go-go' version of a continuous performance task, coupled with a passive attending phase in which the subjects merely watched the stimuli of the task. The three age groups featured a constellation of ERP components that shared the same general morphological appearance and distribution, but differences were seen with respect to latencies and amplitudes. Consistent with other studies, there was an inverse relationship with respect to age and peak latencies of the major passive and effortful components. With respect to peak amplitudes, however, the most impressive changes with age were observed in the passive processing components. For example, the P150 and P250 components presented greater amplitudes in children, whereas the N200 component presented its greatest amplitude in adults. While passive in the sense that their appearances were independent of the 'decision-making' process, these components were found to be upwardly adjustable by effort. The late positive component was found to be a combination of a passive P350 and an effortful P450. The P350 component was judged to be largely passive in character as it was well developed in subjects of all age groups when passively attending to the visual stimuli. There was no marked amplitude difference between the child and adult P450 components, but the components peaked in amplitude later in the children. Finally, the children's ERPs featured a distinct frontal negativity (FN) that was present in the Passive phase, but greatly enhanced during the Effortful phase. This study, as have many others, showed that there are reliable developmental changes in the components of visual ERPs. Therefore, the characteristics of the various components of cognitive ERPs may be effective markers of neurodevelopmental status, especially of those neuronal systems vital to attentional processing and effort regulation.

Adolescent↗
PubMed1997

Two pregnant women with vomiting and fits.

Two women with hyperemesis gravidarum were first seen with a short history of confusion diplopia, unsteadiness, and fits caused by Wernicke's encephalopathy. The neurologic presentation had been precipitated by a carbohydrate load inadvertently administered without vitamin supplementation. We stress the importance of prescribing thiamine supplements to all women with prolonged vomiting during pregnancy.

Adult↗