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Biomedical subjects

R Benjamin

Publications and source records attributed to R Benjamin.

At least 19 recordsLinked to original sources
PubMed2001

Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer.

PURPOSE: We investigated the safety and pharmacokinetics of a recombinant human monoclonal antibody to vascular endothelial growth factor (rhuMAb VEGF) in patients with cancer. PATIENTS AND METHODS: Cohorts of patients with metastatic cancer having failed prior therapy entered a phase I trial of rhuMAb VEGF administered by a 90-minute intravenous infusion at doses from 0.1 to 10.0 mg/kg on days 0, 28, 35, and 42. Patients underwent pharmacokinetic sampling on day 0 and had serum samples obtained during the subsequent 28 days. Response assessment was carried out on days 49 and 72. RESULTS: Twenty-five patients with a median Eastern Cooperative Oncology Group performance status of 0 were accrued. There were no grade III or IV adverse events definitely related to the antibody. There were three episodes of tumor-related bleeding. Infusions of rhuMAb VEGF were well tolerated without significant toxicity. Grades I and II adverse events possibly or probably related to study drug included asthenia, headache, and nausea. Pharmacokinetics revealed a linear profile with a half-life of 21 days. There were no objective responses, though 12 patients experienced stable disease over the duration of the study. CONCLUSION: rhuMAb VEGF was safely administered without dose-limiting toxicity at doses ranging up to 10 mg/kg. Multiple doses of rhuMAb VEGF were well tolerated, and pharmacokinetic studies indicate that doses of > or = 0.3 mg/kg have a half-life similar to that of other humanized antibodies. Subsequent trials will explore rhuMAb VEGF alone and in combination chemotherapy.

Adult↗
PubMed1999

Accretion of low-metallicity gas by the Milky Way.

Models of the chemical evolution of the Milky Way suggest that the observed abundances of elements heavier than helium ('metals') require a continuous infall of gas with metallicity (metal abundance) about 0.1 times the solar value. An infall rate integrated over the entire disk of the Milky Way of approximately 1 solar mass per year can solve the 'G-dwarf problem'--the observational fact that the metallicities of most long-lived stars near the Sun lie in a relatively narrow range. This infall dilutes the enrichment arising from the production of heavy elements in stars, and thereby prevents the metallicity of the interstellar medium from increasing steadily with time. However, in other spiral galaxies, the low-metallicity gas needed to provide this infall has been observed only in associated dwarf galaxies and in the extreme outer disk of the Milky Way. In the distant Universe, low-metallicity hydrogen clouds (known as 'damped Ly alpha absorbers') are sometimes seen near galaxies. Here we report a metallicity of 0.09 times solar for a massive cloud that is falling into the disk of the Milky Way. The mass flow associated with this cloud represents an infall per unit area of about the theoretically expected rate, and approximately 0.1-0.2 times the amount required for the whole Galaxy.

Astronomical Phenomena↗
PubMed1998

Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases.

Our results with concurrent biochemotherapy in patients with stage IV melanoma have been encouraging. Based on these data, we conducted a phase II study to determine the clinical and histological response rate to neoadjuvant concurrent biochemotherapy in patients with local-regional metastases of cutaneous melanoma (stage III). A total of 65 patients with biopsy-proven, measurable and potentially resectable local-regional disease (nodal, satellite/in-transit metastases and/or local recurrence) were treated with cisplatin 20 mg/m2 intravenously (i.v.) on days 1 to 4, vinblastine 1.5 mg/m2 i.v. on days 1 to 4, dacarbazine 800 mg/m2 i.v. on day 1 only, interleukin-2 9 MIU/m2 per day i.v. by 96 h continuous infusion on days 1 to 4, and interferon-alpha 2a 5 MU/m2 subcutaneously on days 1 to 5, repeated every 3 weeks. Patients underwent surgery after two to four courses of biochemotherapy. Those with tumour regression after two preoperative courses received two additional postoperative courses. Of the 64 patients assessable for clinical response, 28 (44%) had a partial response. Of the 62 patients whose response was assessed histologically, four (6.5%) had no evidence of viable tumour in the surgical specimen (pathological complete remission, pCR) and 27 (43.5%) had a partial response, giving an overall response rate of 50%. Tumour burden did not correlate with response, although patients who achieved a pCR had a significantly lower tumour burden (P = 0.02). Our phase II study indicates that neoadjuvant biochemotherapy is an active treatment for melanoma patients with local-regional metastases. However, it is unclear if biochemotherapy is more active than chemotherapy alone; phase III randomized trials are ongoing to answer this question in patients with stage IV disease.

Adolescent↗
PubMed1998

The parenting experiences of mothers with dissociative disorders.

This article presents a qualitative analysis of the experience of parenting of mothers with dissociative disorders. This analysis was performed to complement the quantitative analysis of problems of mothers with dissociative disorders that Benjamin, Benjamin, and Rind (1996) presented previously. They found that the functioning of these mothers, as well as their subjective experience of mothering, was poorer than that of either clinical or nonclinical control mothers. Our goal was to provide a clearer, richer picture of their problems in parenting. Using the mothers' own words, we describe how the five symptom areas of dissociation (amnesia, depersonalization, derealization, identity confusion, and identity alteration) impeded their parenting efforts. We conclude with a discussion of the necessity of addressing parenting in the treatment of client-mothers with dissociative disorders.

Adaptation, Psychological↗
PubMed1996

Phase II study of paclitaxel in patients with previously treated osteosarcoma and its variants.

BACKGROUND: Patients with osteosarcoma and its variants who did not respond to standard chemotherapy including doxorubicin, ifosfamide, cisplatin, and high dose methotrexate were treated with paclitaxel so that its therapeutic activity in these patients could be determined. METHODS: We conducted a Phase II study of paclitaxel in patients with conventional osteosarcoma (10), malignant fibrous histiocytoma of the bone (3) and dedifferentiated chondrosarcoma (2) whose disease had progressed after prior standard chemotherapy including doxorubicin, cisplatin, ifosfamide, and high dose methotrexate. Paclitaxel was administered at a starting dose of 175 mg/m2 as a 24-hour infusion with standard premedication every 21 days or upon hematologic recovery (absolute granulocyte count [AGC] > 1500/microliters, platelets > 100,000/microliters). Neupogen was not used routinely. The study was conducted based on a two-stage design. A total of 17 patients were entered into the protocol. Two were ineligible since they had Ewing's sarcoma. Responses were assessed radiographically and pathologically when feasible, using standard criteria. RESULTS: Fifteen eligible patients were treated in the first stage of the study. Median age of the patients was 31 years (range, 19-61 yrs). There were 8 females and 7 males with a Zubrod performance status of 0 or 1. One patient achieved a mixed response and 14 developed progressive disease. Median AGC nadir was 0.3, on Day 13, lasting 5 days. Median platelet nadir was 134, on Day 8. There were no Grade III or IV nonhematologic toxicities and no deaths related to treatment. CONCLUSIONS: Paclitaxel, at this dose and schedule, is well tolerated but inactive in this patient population.

Adult↗
PubMed1996

Apolipoprotein E genotype and Alzheimer's disease in an elderly Norwegian cohort.

Apolipoprotein E (Apo E) genotyping was performed on an autopsy cohort of neuropathologically verified non-demented controls and subjects with Alzheimer's disease (AD) resident in nursing homes in the Oslo area. AD was associated with a significantly increased frequency of the Apo E epsilon 4 allele; the frequency of the epsilon 2 and epsilon 3 alleles was lower in AD but not significantly so. Age at death in the control group and the AD group did not differ significantly; neither did age at death nor age at onset of dementia in AD vary according to Apo E genotype, though tendencies towards an earlier age at death was seen in individuals with epsilon 4/4 and earlier age at onset dementia in the presence of an epsilon 4 allele and a later age of onset the presence of an epsilon 3 allele were seen. Possession of an epsilon 2 allele had no effect on age at onset of dementia or age at death. Among the possible genotypes there was a trend towards a progression of earliest onset epsilon 4/4, epsilon 2/4, epsilon 3/4, epsilon 3/3, epsilon 2/3 latest onset of dementia and longest duration epsilon 2/4, epsilon 4/4, epsilon 3/4, epsilon 3/3, epsilon 2/3 to shortest duration of dementia.

Age of Onset↗
PubMed1996

Molecular biology of APO E alleles in Alzheimer's and non-Alzheimer's dementias.

Current research into the aetiology of the dementias is focused upon genetic factors which give rise to the disease process. Recently the Apolipoprotein E gene (APO E) and in particular the epsilon 4 allele has been shown to be a risk factor for late onset Alzheimer's disease (AD) where there is an increased frequency of the epsilon 4 allele. The epsilon 4 allele has also been shown to reduce the age at onset of dementia in AD in a dose dependent manner, with the epsilon 2 allele having an opposing effect. We have genotyped a large series of clinically and neuropathologically confirmed cases of AD and found the expected increase in the Apolipoprotein epsilon 4 allele frequency when compared to a control population. Similarly, in Lewy Body Dementia (LBD) an increased epsilon 4 frequency is also found though a normal epsilon 2 frequency exists, unlike in AD where the epsilon 2 frequency is reduced. No changes in APO E allele frequencies were found in presenile AD, Parkinson's disease with or without dementia, or in Down's syndrome. No association was found between any of the APO E alleles and the histopathological indices of AD, cortical senile plaques and neurofibrillary tangles, in any disease category. Neurochemical indicators of AD, loss of choline acetyltransferase activity was also unaffected by APO E genotype. Whilst their appears to be a strong association between the APO E allele and AD and also in LBD, other related neurodegenerative disorders associated with dementia do not show such a linkage. Changes in the epsilon 2 allele frequency may indicate a genetic difference between AD and LBD. The epsilon 4 allele does not appear to influence the burden of AD type pathology and this is particularly relevant given the relative lack of NFT in LBD indicating that factors other than SP or NFT may govern the onset of dementia.

Alleles↗
PubMed1996

Extraction and use of X-ray specific density following object-based three-dimensional reconstruction.

Given a set of three-dimensionally reconstructed objects and the source X-ray images from which the reconstructions have been derived, it is shown how the uniform or smoothly varying X-ray specific densities (i.e. CT coefficients) of these objects can be derived. It is considered how that information can be used, inter alia, to synthesise conventional X-ray images (with unconventional refinements), or to compute tomographic slice images (but without textural information.

Humans↗
PubMed1996

Object-based three-dimensional X-ray imaging.

A form of three-dimensional X-ray imaging, called Object 3-D, is introduced, where the relevant subject material is represented as discrete 'objects'. The surface of each such object is derived accurately from the projections of its outline, and of its other discontinuities, in about ten conventional X-ray views, distributed in solid angle. This technique is suitable for many applications, and permits dramatic savings in radiation exposure and in data acquisition and manipulation. It is well matched to user-friendly interactive displays.

Humans↗
PubMed1996

Dissociative mothers' subjective experience of parenting.

This study examined to what extent the symptoms of dissociative mothers interfered with their parenting and their subjective experiences of mothering. A group of 54 dissociative inpatient or day-patient mothers, 20 nondissociative inpatient mothers, and 20 hospital staff mothers were screened for Dissociative Disorders using the Structured Clinical Interview for Dissociative Disorders (SCID-D). They were then asked to fill out a self-report questionnaire on various aspects of mothering. This questionnaire, the Subjective Experiences of Parenting Scale (SEPS), examined 14 parenting characteristics: parenting partner support; relative support; abusiveness towards the child; extent to which symptoms interfered with parenting; constructive parenting traits; supportive versus hurtful discipline; extent of showing affection; ability to express affection; attachment behaviors; cognitive distortions; regulation of anger; self versus mother in parenting; subjective experience of mothering; and actions to promote the developmental growth of the child Dissociatives presented significantly more negative parenting behavior and related attributes than staff controls on 13 of the 14 parenting characteristics. Compared to nondissociative patients, the dissociative cohort presented poorer parenting behavior and related attributes on 9 of the 14 characteristics. Overall, the dissociatives experienced more problems with parenting attitudes and behaviors than either comparison group. Dissociative mothers manifested affective, behavioral, and cognitive difficulties in parenting.

Adult↗
PubMed1996

Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery pain.

To study the analgesic efficacy of enadoline, a selective agonist of the kappa-opioid receptor, a double-blind, randomized comparison was made of enadoline versus placebo and a combination of acetaminophen-codeine in patients with pain after surgical extraction of impacted molar teeth. An initial study involving a comparison of enadoline, a combination, and placebo failed to show any analgesic effect of enadoline. Therefore, a second study with the same design but using higher doses of enadoline was conducted. Despite continued safety and tolerability even at the higher doses, enadoline could not be shown to be superior to placebo. The acetaminophen-codeine combination was significantly more effective than enadoline or placebo. Enadoline did not show analgesic efficacy in this study. Possible reasons for this lack of efficacy are discussed.

Acetaminophen↗
PubMed1996

Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain.

Enadoline, a selective agonist of the kappa-opioid receptor, was studied for its analgesic efficacy in patients with pain after obstetric or gynecologic surgery. An initial study involving a comparison of enadoline (2, 5, 15 micrograms), an acetaminophen-codeine (ACET/COD) combination, and placebo showed all treatments to be ineffective analgesics. Therefore, a second study with the same design but using higher doses of enadoline (15 and 25 micrograms) and replacing ACET/COD with morphine 10 mg i.m. was conducted. Enadoline 25 micrograms produced similar pain relief to that of morphine, although of shorter duration, and better than enadoline 15 micrograms or placebo. However, enadoline was associated with dose-limiting neuropsychiatric adverse events, which led to early termination of the study.

Abdomen↗
PubMed1995

Effect of apolipoprotein E genotype on Alzheimer's disease neuropathology in a cohort of elderly Norwegians.

A cohort of elderly Norwegians dying in nursing homes in the Oslo region have been genotyped for the Apolipoprotein E (ApoE) gene. Alzheimer's disease (AD) cortical neuropathology and clinical evidence of dementia were used to assign cases without evidence of other confounding neuropathology. Senile plaque (SP) and neurofibrillary tangle (NFT) densities in frontal, temporal and parietal cortex were then correlated with ApoE genotype to determine any relationship between ApoE genotype and AD pathology. Comparisons with ApoE epsilon 3, epsilon 4 and epsilon 2 allele dosage failed to show any significant effect on cortical SP densities in any cortical area. NFT densities were increased by epsilon 4 allele dosage in the frontal cortex but not in other cortical regions. A reduction was seen in cortical NFT densities with epsilon 2 allele, though again this was not consistently significant in any of the groups. The epsilon 3 allele failed to show any consistent effect on cortical NFT densities. Assessment by individual genotypes showed epsilon 2/3 < epsilon 2/4 < epsilon 3/3 < epsilon 3/4 < epsilon 4/4 which had highest cortical NFT densities in all areas. By genotype, SP densities were generally of the order epsilon 2/4 < epsilon 2/3 < epsilon 3/3 < epsilon 4/4 < epsilon 3/4 though in none of the groups was this significant. Duration of disease showed no consistent effect on neuropathological burden. ApoE genotype may have an effect on determining whether individuals suffer from AD and the age at onset of disease but may only have a minimal effect on pathology burden.

Aged↗
PubMed1995

Characterization of a messenger RNA polynucleotide vaccine vector.

We have constructed mRNA transcripts encoding luciferase and human carcinoembryonic antigen (CEA) which are capped, polyadenylated, and stabilized by human beta-globin 5' and 3' untranslated regions. The mRNA construct encoding human CEA directed CEA expression in mouse fibroblasts in vitro following liposome-mediated transfection. The luciferase encoding mRNA transcripts mediated luciferase expression in vivo following i.m. injection. Based on the demonstration of protein expression in vitro and in vivo, the feasibility of using such a vector as a tumor vaccine was examined. In this pilot study, seven mice received 50 micrograms mRNA transcripts encoding CEA twice weekly for 5 weeks by i.m. injection followed by challenge with syngeneic, CEA-expressing tumor cells. This dose and schedule "primed" an immune response to CEA. Five of seven mRNA-immunized mice demonstrated anti-CEA antibody 3 weeks after tumor challenge whereas control mice had no evidence of antibody response. This strategy might be particularly useful to induce an immune response to a proto-oncogene product or growth factor which poses a risk of inducing malignant transformation consequent to prolonged protein expression.

Animals↗
PubMed1995

Effects of apolipoprotein E genotype on cortical neuropathology in senile dementia of the Lewy body and Alzheimer's disease.

Apolipoprotein E (APO E) genotypes were determined in a UK population of neuropathologically confirmed control cases, and in cases of Lewy body dementia (SDLT) and late onset Alzheimer's disease (AD). APO E epsilon 4 allele frequency was significantly elevated in both SDLT and AD groups with a concomitant reduction in the APO E epsilon 3 allele frequency. The epsilon 2 allele frequency in the AD group was only 25% of the control population, though because of the relatively small sample size this reduction was not significant; the epsilon 2 allele frequency in the SDLT group was normal. No significant association was found between senile plaque density and neurofibrillary tangle density in the neocortex and APO E allele dose in either SDLT or AD. Although the possession of APO E epsilon 4 is associated with an increased risk of developing SDLT and AD, actual APO E genotype does not appear to affect the burden of pathology.

Alleles↗