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Biomedical subjects

R Bell

Publications and source records attributed to R Bell.

At least 127 records · Page 7Linked to original sources
PubMed1996

Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group.

BACKGROUND: Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. METHODS: Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. RESULTS: Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. CONCLUSIONS: Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.

Aged↗
PubMed1996

Effects of the 5-HT1A antagonist (+)-WAY-100135 on murine social and agonistic behavior.

Compounds previously identified as 5-HT1A antagonists have subsequently been demonstrated to possess partial agonistic properties in models assessing somatodendritic autoreceptor function. This study examined the influences of (+)-WAY-100135, claimed to be the first selective 5-HT1A antagonist, on offensive behaviour in male mice. Employing a resident-intruder paradigm, administration of (+)-WAY-100135 (1.0-10.0 mg/kg s.c.) enhanced elements of resident offensive behaviour at 2.5 and 5.0 mg/kg but reduced such behaviour at 10.0 mg/kg. In comparison, resident defensive postures remained unchanged except for a significant increase in defensive sideways behaviour at 10.0 mg/kg. These effects were accompanied by reduced rearing behaviour across the dose range tested. Attend/approach behaviour was significantly reduced at the lowest, but increased at the highest, doses tested. Such results may reflect response competition rather than concomitant motor impairment. Given the dynamic behavioural interactions occurring in this paradigm, the increased offensive behaviour of the resident mice leads to enhanced defence and counter-attack by the intruder conspecifics. The results are discussed with reference to the current literature concerning the behavioural effects of other 5-HT1A antagonists.

Agonistic Behavior↗
PubMed1996

Soft tissue sarcoma of the extremity. Limb salvage after failure of combined conservative therapy.

PURPOSE: To assess the results of salvage therapy using surgery alone or surgery and re-irradiation for patients with locally recurrent extremity soft tissue sarcoma (STS) following conservative surgery and radiotherapy. MATERIALS AND METHODS: 25 patients with locally recurrent STS after conservative surgery and irradiation were assessed between 1990 and 1995. Two patients with concurrent systemic relapse were treated palliatively. Seven patients were not candidates for conservative re-excision and underwent amputation, 11 patients underwent conservative resection without irradiation. Seven of these patients relapsed, and five went on to receive combined conservative surgery and re-irradiation. A further five patients initially received combined retreatment, for a total of ten patients treated with combined conservative surgery and re-irradiation. Six of these ten patients were treated with brachytherapy alone, one with brachytherapy and external beam therapy, and three with external beam therapy alone. The median retreatment dose was 49.5 Gy (range 35-65 Gy), and the median cumulative soft tissue dose was 100 Gy (range 93-120 Gy). RESULTS: The median follow-up from the most recent treatment is 24 months (range 7-42 months). At the last follow-up 14 patients are alive and disease free; two are alive with local disease and four with systemic disease, and five are dead of disease. Overall local control is 19/23 (91%). The local control for patients treated with conservative excision without irradiation is 4/11 (36%) and for conservative excision with re-irradiation 10/10 (100%). Six (60%) of these patients experienced significant post-irradiation would-healing complications, but three have recovered fully. Functional scores for the entire treated group are significantly lower after treatment, as are those for patients undergoing combined surgery and re-irradiation, but 70% of those treated with conservative surgery and re-irradiation and a good or excellent post-treatment functional score. CONCLUSIONS: Combined conservative surgery and re-irradiation provided superior local control to local re-excision alone and a functional outcome superior to amputation. Combined treatment with re-irradiation should be considered the primary salvage therapy for patients who fail combined therapy and who are suitable for conservative re-excision. Systemic relapse is a significant problem, and optimal therapy should minimize the risk of local relapse after the initial therapy. Eighteen patients (72%) had a history of intralesional excision as their initial intervention, and suggests that inappropriate initial management is a risk factor for relapse after combined conservative therapy. Improvements in therapy must include the appropriate education of the primary care physicians.

Adult↗
PubMed1996

Chordoma: long-term follow-up after radical photon irradiation.

PURPOSE: To retrospectively analyze the long term results of treatment and the patterns of failure for patients with chordoma of the sacrum, base of skull and mobile spine treated predominantly with postoperative photon irradiation. MATERIALS AND METHODS: Forty-eight adult patients with chordoma of the sacrum (23), base of skull (20) or mobile spine (5), were seen between 1958-1992. Forty-four were referred post operatively with overt disease and 31 of these were irradiated with conventionally fractionated radiation to a median dose of 50 Gy/25 fractions/5 weeks (range 25-60 Gy). Eight received a hyperfractionation protocol of 1 Gy, 4 hourly, 4 times a day (median 40 Gy/44 fractions/14 days), two sacral patients were treated with a hypofractionation protocol and three cases with skull base tumours were referred elsewhere for proton therapy. Endpoints measured were survival from diagnosis, objective response rate, symptomatic response rate and clinical or radiological progression-free survival from radiotherapy. RESULTS: Median survival was 62 months (range 4-240 month) from diagnosis with no difference between clival and non-clival presentations. One complete and no partial responses were identified in 23 assessable patients. A subjective response was recorded for 12/14 (85%) with pain and 10/23 (45%) with neurological signs or symptoms, and the median time to progression for those with overt disease was 35 months (range 5-220 months). There was no survival advantage to patients receiving radiation doses > 50 Gy (median 60 Gy) compared to doses < 50 Gy (median 40 Gy). There was no difference between the conventional or hyperfractionation regimens with respect to the degree or duration of symptomatic response, or in progression-free survival. Fourteen patients who progressed after irradiation were retreated with surgery (6), irradiation (7) or both modalities (1). Median survival after retreatment was 18 months, and the only two symptomatic responses seen were with reirradiation, and after failure of relatively low dose initial therapy. At last follow-up, 35 were dead of or with disease, seven are alive with disease, and two are disease-free. Thirty-eight had local disease persistence as the sole site of failure, and four developed distant metastases initially or subsequently. DISCUSSION: Overt residual chordoma is rarely cured with conventional external beam irradiation, but treatment does provide useful and prolonged palliation of pain for most patients. Chordoma is a disease with low metastatic potential, and better local control may improve survival. Complete resection rates may be improved for patients with sacral disease by using planned excisions in centres experienced in treating this rare disease. Because radiation therapy may prove to be more successful in controlling microscopic disease, it should be considered as a pre- or postoperative adjuvant to a macroscopically complete resection. Patients with skull base disease should also be resected in centres specializing in this surgery, but complete excision is unlikely. These patients will not obtain local control with conventional photon irradiation, and suitable patients should be considered for irradiation with stereotactic photon or particle beam therapy. For patients who progress after irradiation, there is limited symptomatic benefit to retreatment with surgery or reirradiation, and this should be limited to treating life-threatening complications.

Chordoma↗
PubMed1996

What are popular magazines telling young women about pregnancy, birth, breastfeeding and parenting?

Popular magazines are an important source of health and lifestyle information for young women. This study aimed to investigate the extent and nature of the information presented about pregnancy, birth, breastfeeding and parenting. Content analysis of four monthly popular magazines over a period of one year reveals that references to pregnancy, birth and breastfeeding were contained in thirty-six (75%) of the forty-eight magazines reviewed. Many of these references represent a useful source of information, but there are a number of meddlesome or destructive themes, specifically weight gain in pregnancy, lack of control in your life, the 'agony' of childbirth and the negative impact childbirth has on marital relationships and career.

Breast Feeding↗
PubMed1996

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

BRCA2 Protein↗
PubMed1996

Low incidence of BRCA2 mutations in breast carcinoma and other cancers.

Inherited mutant alleles of familial tumour suppressor genes predispose individuals to particular types of cancer. In addition to an involvement in inherited susceptibility to cancer, these tumour suppressor genes are targets for somatic mutations in sporadic cancers of the same type found in the familial forms. An exception is BRCA1, which contributes to a significant fraction of familial breast and ovarian cancer, but undergoes mutation at very low rates in sporadic breast and ovarian cancers. This finding suggests that other genes may be the principal targets for somatic mutation in breast carcinoma. A second, recently identified familial breast cancer gene, BRCA2 (refs 5-8), accounts for a proportion of breast cancer roughly equal to BRCA1. Like BRCA1, BRCA2 behaves as a dominantly inherited tumour suppressor gene. Individuals who inherit one mutant allele are at increased risk for breast cancer, and the tumours they develop lose the wild-type allele by heterozygous deletion. The BRCA2 coding sequence is huge, composed of 26 exons that span 10,443 bp. Here we investigate the rate of BRCA2 mutation in sporadic breast cancers and in a set of cell lines that represent twelve other tumour types. Surprisingly, mutations in BRCA2 are infrequent in cancers including breast carcinoma. However, a probable germline mutation in a pancreatic tumour cell line suggests a role for BRCA2 in susceptibility to pancreatic cancer.

BRCA2 Protein↗
PubMed1996

Nutritional effect of calcium supplementation by skim milk powder or calcium tablets on total nutrient intake in postmenopausal women.

The effect of different types of calcium supplements on total nutrient intake has not been studied. The effect of dietary calcium supplementation (calcium tablets or skim milk powder) on nutrient intake in 64 postmenopausal women was studied in a 4-y longitudinal study consisting of 2 y of intervention and 2 y of follow-up. Subjects also received advice on how to reduce their consumption of high-fat and cholesterol-rich foods. Analysis of 4-d weighed diet records at 1 y showed that calcium intakes from the milk-powder supplement (1618 +/- 213 mg) and calcium tablets (1718 +/- 257 mg) were above recommended dietary intakes (RDI), and dietary fat intake and plasma cholesterol were significantly reduced compared with baseline values. The subjects supplemented with milk powder had higher intakes of several nutrients, including protein and zinc, compared with the subjects given calcium tablets. A greater proportion of subjects using the milk-powder supplement achieved > or = 70% of the RDI for zinc compared with tablet-supplemented subjects during the intervention study. Subjects were advised to continue with supplementation at the end of the intervention study. Thirty-nine subjects were available for follow-up. The mean (+/- SD) calcium intake for the milk-powder group (942 +/- 434 mg) was below the RDI and significantly lower than that of the calcium-tablet group (1346 +/- 512 mg). These data suggest that advice on dietary calcium supplementation and fat reduction had a beneficial effect on the nutrient intakes of postmenopausal women but compliance outside of a control trial by women taking calcium tablets was higher than that by women taking milk powder. Thus, strategies to encourage women to increase calcium intake can be introduced without significant deleterious effects on other aspects of the diet.

Administration, Oral↗
PubMed1996

Locations of herpes simplex virus type 2 glycoprotein B epitopes recognized by human serum immunoglobulin G antibodies.

Herpes simplex virus type 2 (HSV-2) glycoprotein B (gB-2) gene segments were expressed as recombinant proteins in Escherichia coli. gB-2 recombinant proteins were reacted with human serum immunoglobulin G (IgG) antibodies in Western immunoblot assays. Initially, samples were tested for the presence of HSV-1-specific antibodies and HSV-2-specific antibodies by using HSV-infected cell lysates as antigen targets in Western blot assays. Serum samples that contained HSV-2-specific IgG (n = 58), HSV-1-specific IgG (n = 33), or no detectable HSV antibodies (n = 31) were tested for reactivities with the gB-2 recombinant proteins. In 58 of 58 samples that contained HSV-2-specific IgG, antibodies were present that reacted strongly with a gB-2 amino-proximal segment between amino acids (aa) 18 and 75. Three of 33 serum samples that contained HSV-1- and not HSV-2-specific IgG (as defined by the HSV lysate Western blot assay) reacted with this segment. Both HSV-2 antibodies and HSV-1 antibodies reacted strongly with a carboxy-terminal gB-2 segment between aa 819 and 904; a second minor cross-reactive region was mapped to a gB-2 segment between aa 564 and 626. The gB-2 segment from aa 18 to 75 may constitute a useful reagent for the virus type-specific serodiagnosis of HSV-2 infections. Further studies will be required to determine the relative sensitivities and specificities of the assay for gB-2 aa 18 to 75, HSV gG assays, and HSV lysate Western blot assays for detecting virus type-specific antibody responses in acute and chronic HSV-2 infections.

Amino Acid Sequence↗
PubMed1996

Residual disease following unplanned excision of soft-tissue sarcoma of an extremity.

Sixty-five patients who had been referred to our unit for additional management after an unplanned excision of a soft-tissue sarcoma of an extremity at another institution were studied retrospectively to determine the prevalence of residual tumor and to identify factors that predict which patients will have a tumor following such an excision. Unplanned excision was defined as excisional biopsy or unplanned resection of the lesion without benefit of preoperative imaging and without regard for the necessity to resect the lesion with a margin of normal tissue. In each patient, histological evaluation of the specimen removed at the unplanned excision had demonstrated positive resection margins, but postoperative physical examination on our unit revealed no gross evidence of residual tumor and no tumor was identified on cross-sectional imaging of the local site. Patients who had evidence of residual disease on physical examination or on imaging were thought to have definite evidence of sarcoma at the site of the operative wound and were therefore excluded from the study. After multidisciplinary consultation, all patients had a repeat resection at our cancer center. Extensive pathological sampling of the specimen from this second procedure was carried out, with sections obtained at mean intervals of 1.2 +/- 0.7 centimeters. Nodules initially thought to indicate disease were identified grossly in twenty-seven (42 percent) of the sixty-five patients, but histological evaluation confirmed the presence of tumor in only sixteen (59 percent). Histological evidence of sarcoma was identified in seven additional patients in whom gross nodules were not apparent in the specimen. Thus, sarcoma was identified in a total of twenty-three (35 percent) of the sixty-five patients. The mean duration of follow-up was forty-six months (range, twenty-four to eighty months; median, thirty-nine months). The margins of the second resection were positive in nine (39 percent) of the twenty-three patients who had residual sarcoma. Five (22 percent) of the twenty-three had a local recurrence. Four of the five patients who had a local recurrence had positive margins on repeat resection. This rate of local recurrence (five of twenty-three patients) was significantly higher than that in the remainder of our patients who had a soft-tissue sarcoma of an extremity (sixteen [7 percent] of 227) (p = 0.03). There was no association between the detection of sarcoma at the second procedure and the initial size or grade of the tumor, the use of irradiation preoperatively, or the interval between the initial, unplanned excision and referral to our cancer center. These data indicate that it is not possible to predict which patients will have residual tumor at the site of the operative wound. Therefore, it is prudent to advise repeat excision for all patients who have had an unplanned excision of a soft-tissue sarcoma of an extremity. Unplanned excision complicates decision-making in the treatment of this disease and should be avoided.

Biopsy↗
PubMed1995

Long-term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell tumors of bone.

PURPOSE: Giant cell tumors of the bone are rare and have variable presentations and natural history. There may be significant functional sequelae as a result of their locally aggressive nature or as a result of treatment. We reviewed the long-term results of radiotherapy for high risk giant cell tumors to assess: the efficacy of radiotherapy and the potential late toxicity of treatment, and to determine indications for radiation treatment. METHODS AND MATERIALS: This report is a retrospective review of 21 localized giant cell tumors of the bone treated with radiotherapy between 1959 and 1991. Radiation was used in the primary management of 13 cases and for recurrent disease in eight cases. In the primary cases, two received radiotherapy as the sole modality (including a massive pelvic lesion and an advanced maxillary sinus tumor with orbital and pterygoid invasion), and in the other 11, 3 had gross residual disease following surgery and 8 had microscopic residual disease. Of eight recurrent cases, five were treated with radiotherapy alone and three with combined surgery and radiation. Sites of origin included extremity bones in nine cases, pelvis in six, spine in four, and skull in two. Extraosseous disease was apparent in 18 tumors and extended to contiguous structures in 14 (including four cases of spinal cord compression, three cases of sacral plexopathy, and one patient with temporal lobe invasion). The most common dose regimen was 35 Gy/15 fractions/3 weeks (14 cases), with varying schedules for the remainder. RESULTS: Mean follow-up time was 15.4 years (2 to 35 years). Local control was achieved in 19 of 21 patients with radiotherapy. The two failures were subsequently salvaged for an ultimate control rate of 100%. One of the two radiotherapy failures was a marginal failure and was subsequently salvaged with combined surgery and radiotherapy. No patient died of giant cell tumor. Radiotherapy was well tolerated, with no serious late toxicity. There were no cases of malignant transformation or radiation-induced cancer. CONCLUSION: Long-term results in this series indicate that radiotherapy in modest doses (35 Gy in 15 fractions or equivalent) is a safe and effective option for primary and recurrent giant cell tumors of the bone. Radiotherapy should be used if surgery would result in significant functional morbidity and should be considered in select sites where the probability of recurrence is high and there is potential for significant morbidity from tumor relapse or subsequent surgery.

Adolescent↗
PubMed1995

No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia.

DeLisi et al. (1994b) have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male-to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped using the PCR and LOD scores calculated using five models of inheritance, including classical dominant recessive and intermediate models. LOD scores were substantially negative for all models examined and analysis for linkage heterogeneity using the LOD2 method showed no significance. Analysis by the nonparametric affected sib-pair method likewise indicated no linkage. We conclude that DXS7 is not a major locus for schizophrenia in our collection of pedigrees.

Family↗
PubMed1995

New spiropiperidines as potent and selective non-peptide tachykinin NK2 receptor antagonists.

The synthesis of a series of 2-(5-fluoro-1H-indol-3-yl)ethyl spiropiperidines is described together with their tachykinin NK2 receptor affinities measured in a rat colon binding assay. Equivalent NK2 receptor binding affinity was observed for the spirooxazolidinone 3-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-1-oxa-3,8-diazaspiro[4.5] decan-2-one (3a), the imidazolidinone 3-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-1,3,8-triazaspiro[4.5 ] decan-2-one (3s), and the pyrrolidinone 2-benzyl-8-[2-(5-fluoro-1H-indol-3-yl)ethyl]-2,8-diazaspiro[4.5]decan -3 - one (3t). Substitution in the phenyl ring of compound 3a produced no significant enhancement in NK2 binding affinity. Replacement of the phenyl ring in 3a with other aromatic rings resulted in a significant loss in binding affinity. Compound 3a was shown to be a potent NK2 receptor antagonist in guinea pig trachea where it also demonstrated 1000-fold selectivity for NK2 receptors over NK1. In the anesthetized guinea pig, compound 3a administered by the intravenous or oral route displayed potent and long-lasting antagonist activity against NK2 receptor agonist induced bronchoconstriction.

Animals↗