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B Anderson

Publications and source records attributed to B Anderson.

At least 37 records · Page 2Linked to original sources

Distant metastases in ovarian cancer: association with p53 mutations.

Distant metastases are unusual occurrences at presentation and during the progression of epithelial ovarian cancer. There are no good clinical predictors of this phenomenon. Because p53 dysfunction is common in ovarian cancer, we chose to investigate whether specific types of mutations predicted a predisposition to distant metastasis. We hypothesized that the complete absence of intact p53 protein as seen with p53 null mutations may be associated with an enhanced tendency to develop distant metastatic disease. The complete coding sequence of 130 tumor DNA samples was screened for p53 mutations by single-strand conformational polymorphism analysis. Abnormal single-strand conformational polymorphism findings were correlated with the specific DNA sequence abnormalities and outcome. Ninety-four (72%) tumors carried p53 mutations. Sixty-two were missense mutations, and 32 were null mutations (6 nonsense mutations, 23 frameshift mutations, and 3 splice-site mutations). Twenty-eight patients were found to have distant metastases (pericardium, brain, parenchymal liver, spleen, or lung) either at presentation or during the course of their treatment. Distant metastases were nearly 8-fold more common in patients whose tumors carried a null mutation (66%) than in those with either missense mutations (8%) or wild-type p53 (8%; P<0.001). When a null mutation was present, 25% of the tumors were associated with distant metastases at initial diagnosis. No individual with wild-type p53 or a missense mutation in the tumor presented with distant metastasis. Tumors with null mutations were more likely to be associated with lymph node metastasis (P = 0.003), advanced stage (stage III/IV; P<0.001) and high grade (grade II/III; P<0.001), at presentation. These tumors progressed with distant metastases more swiftly than did tumors with either missense mutations (mean, 1.18 versus 2.71 years; P = 0.04) or wild-type p53 (3.57 years; P = 0.015). In contrast to the popular dogma, distant metastases in ovarian cancer do not necessarily result from prolonged treatment of disease. They may be predicted to occur early in the disease course due to a specific molecular genetic abnormality: null mutation of the p53 tumor suppressor gene. These findings need to be carefully considered when choosing between regional versus systemic treatment modalities.

Adult

Anatomic asymmetries of the posterior superior temporal lobes: a postmortem study.

OBJECTIVE: To examine for structural asymmetries in the posterior superior temporal lobe at the microscopic level in an effort to explain the gross anatomical and functional asymmetries of this brain region. BACKGROUND: The posterior superior temporal lobe is typically larger on the left and damage to this area frequently results in an aphasia. This has led to the hypothesis that the structural asymmetry determines the functional asymmetry, but no definite confirmation of this hypothesis exists. METHODS: Sixteen men were studied at postmortem. Posterior superior temporal lobe dimensions, gray matter volume, white matter volume, SMI-32 immunopositive neuronal density, and glia cell volume were measured for both the left and right hemispheres. In a subset of eight subjects, myelin sheath and axon diameters were measured with electron microscopy. RESULTS: Posterior superior temporal lobe white matter volume was greater on the left (p = 0.003, t test for dependent samples). This asymmetry did not appear to be the result of an isolated proliferation of glia (p = 0.46, t test for dependent samples), nor the density of cortical to cortical projections neurons in the overlying cortex (p = 0.71, t test for dependent samples). In a subset of eight subjects studied with electron microscopy, axons of the left posterior superior temporal lobe were more thickly myelinated (57 nm [SD = 27] left, 46 nm [SD = 24], p < 0.001, ANOVA). CONCLUSIONS: As axons with thicker myelin sheaths conduct faster and require a greater volume, these results suggest asymmetry of myelination as an explanation for both a left hemisphere dominance for rapid sensory signal processing, leading to a functional asymmetry for language, and a larger left planum temporale.

Axons

The use of laminarias for osmotic dilation of the cervix in gynecological brachytherapy applications.

PURPOSE: Osmotic dilators (laminarias) have been used for gradual nontraumatic dilation of the cervical canal for various intrauterine procedures; however, this technique has not been well accepted in gynecological brachytherapy. The purpose of this study was to evaluate the efficacy of osmotic cervical dilation for brachytherapy in gynecologic cancer patients, without the use of general/regional anesthesia, and to assess patient tolerance, complications, and outcome. METHODS AND MATERIALS: Thirteen brachytherapy procedures were performed in 6 patients with clinical Stages I and II endometrial (5) and Stage IB cervical cancer (1), who were unable to tolerate general/regional anesthesia because of severe medical problems. An osmotic dilator (synthetic laminaria) was inserted into the cervical os 10-12 h before each brachytherapy procedure and removed just before the procedure. Standard Fletcher-Suit-Delclos tandem insertions with vaginal colpostats or cylinders were then performed. Degree of cervical dilation, patient discomfort, procedure time, intra- and postoperative complications were recorded, and local control and survival were assessed. Median follow-up was 31 months (range: 8-35 months). RESULTS: The diameter of the dilated cervical os after laminaria removal was adequate (> or = 5 mm) for tandem insertion, and no additional mechanical dilation was required in all but one procedure (1 of 13). All procedures were performed without general/regional anesthesia. The mean duration of the procedures was 44 min (range, 20-60 min). Discomfort was minimal in all cases. There were no intra- or postoperative complications. All patients maintained local control until death (1 of metastatic disease, 2 of intercurrent disease) or last follow-up (2 with no evidence of disease, 1 alive with metastatic disease). CONCLUSION: This preliminary study suggests that osmotic cervical dilation with a synthetic laminaria is a useful technique to facilitate intrauterine tandem insertion in patients who cannot tolerate general/regional anesthesia. This technique may reduce treatment-associated morbidity, shorten procedure time, and allow the delivery of adequate radiation therapy in this uncommon but challenging patient population.

Adenocarcinoma

Primary ovarian sarcoma: analysis of prognostic variables and the role of surgical cytoreduction.

BACKGROUND: Data regarding the value of cytoreduction and cell histology in ovarian sarcomas are limited. The goal of this study was to assess the value of surgical cytoreduction, preoperative CA 125 levels, stage, histology, and platinum-based chemotherapy in the primary treatment of ovarian sarcomas. METHODS: A retrospective analysis of 47 women with primary ovarian sarcomas was performed. RESULTS: Forty-one patients (87%) presented with advanced stage disease (International Federation of Gynecology and Obstetrics Stage III or IV). Optimal surgical cytoreduction (< 1 cm residual tumor burden) was achieved in 25 patients (53%). Forty patients (85%) had a malignant mixed müllerian tumor whereas 7 patients had a pure sarcoma. Eighteen women with mixed müllerian tumors had homologous tumors and 22 had heterologous elements. Patients treated with platinum-based chemotherapy were significantly more likely to have a response (P = 0.008) compared with those treated with other regimens. Treatment with platinum-based chemotherapy also showed a survival advantage (P = 0.03). Preoperative CA 125 levels were elevated (> 35 U/mL) in 93% of patients with ovarian sarcomas. A preoperative CA 125 level < 75 U/mL was significantly associated with better survival (P = 0.01). In univariate analysis, other significant predictors of improved survival were early stage (P = 0.04), homologous tumors (P < 0.05), and optimal surgical cytoreduction (P < 0.001). In multivariate analysis of various prognostic variables, optimal surgical cytoreduction (P < 0.001) was the most significant factor, followed by histologic subtype (P < 0.02). CONCLUSIONS: Ovarian sarcomas are rare malignancies with a poor prognosis. All women with suspected ovarian carcinoma or sarcoma should have a preoperative CA 125 level taken. Surgical cytoreduction to a residual tumor burden of < or = 1 cm improves outcome and should be the goal of surgery. Although the optimal consolidation chemotherapy regimen remains unknown, platinum should be included as part of the regimen.

Adolescent

Isolation, sequencing and expression of the gene encoding a major protein from the backteriophage associated with Bartonella henselae.

The gene encoding a 31-kDa major protein (Pap31) associated with the bacteriophage harbored in Bartonella henselae was cloned and sequenced. Analysis of the resulting sequence revealed an open reading frame of 837 nucleotides coding for a protein of 279 amino acids. pap31 was then subcloned downstream of the lacZ promoter in pUC19. pap31 was amplified by polymerase chain reaction, and the linear amplicon was used as template for in-vitro transcription and translation. A protein with an apparent molecular mass of approximately 31 kDa was synthesized from this reaction. Upon analysis of the deduced aa sequence, a potential signal sequence and a consensus signal peptidase cleavage site were identified, indicative that Pap31 is modified posttranslationally, and the mature protein may be targeted to the host membrane.

Amino Acid Sequence

Stressful life events and social rhythm disruption in the onset of manic and depressive bipolar episodes: a preliminary investigation.

BACKGROUND: The association between stressful life events and onset of bipolar episodes is unclear. The association between bipolar episode onset and types of life events that disrupt social routines, and potentially sleep, has not yet been investigated. METHODS: Thirty-nine bipolar patients with primarily manic (n = 20) or depressed (n = 19) index episodes were interviewed with the Bedford College Life Event and Difficulty Schedule to determine the presence of severe events during 8-week pre-onset and control periods. All life events were also rated for degree of social rhythm disruption (SRD). RESULTS: More bipolar subjects experienced at least 1 SRD event and severe event in the pre-onset vs control periods. When subjects were divided into those with manic or depressive onsets, the only significant pre-onset vs control difference was for manic patients with SRD events. Additionally, the proportion of subjects with a pre-onset SRD event was greater for manic than for depressed patients. CONCLUSIONS: We found evidence that life events characterized by SRDs routines are associated with the onset of manic, but not depressive, episodes. Severe events seem to be related to onset of bipolar episodes, although it remains unclear whether severe events relate differentially to depressive and manic onsets.

Adult

Taxol hypersensitivity: rapid retreatment is safe and cost effective.

OBJECTIVE: The aim of this study was to describe a rapid retreatment strategy that is safe and cost effective in ovarian cancer patients with Taxol hypersensitivity reactions. METHODS: A retrospective review of 91 women receiving Taxol-based chemotherapy at the University of Iowa Hospitals and Clinics between October 1991 and July 1996 was performed. All patients who developed hypersensitivity reactions to Taxol were identified and their treatment course and outcome were reviewed. RESULTS: Seven women (7.7%) developed hypersensitivity reactions. All received standard premedications consisting of corticosteroids and histamine blockers. Six of the seven were rechallenged with the original Taxol solution starting at a slower rate. In these cases the infusion was completed within 24 h and none of these patients had a reaction in subsequent courses. One patient was not retreated due to the severity of her reaction during a 3-h infusion. CONCLUSION: Retreatment with the original Taxol solution is safe and cost effective in most patients with hypersensitivity reactions. Retreatment with Taxol should be completed within 24 h. A schema for retreatment is presented.

Adrenal Cortex Hormones

Recreational-outdoor burns: the impact and severity--a retrospective review of 107 patients.

INTRODUCTION: Campfires, bonfires and barbecues play a prominent role in outdoor activities and serve a variety of decorative and functional purposes. Given all of it's various forms, uses and benefits, the outdoor fire can turn dangerous in a matter of seconds: a stumble or fall (the child running that trips) leads to direct contact with the flames and subsequent burn injury. With it's everyday occurrence, we were surprised to find a paucity of information regarding this type of burn in the literature, including the NBIE analysis. METHODS: A retrospective review of 107 patients admitted to the Maricopa Medical Bum Center, from 1987 to 1996, was conducted. Each chart was analyzed for the patient demographics, mechanism of injury, percent total body surface area burned, operative versus non-operative treatment and overall outcome. RESULTS: An average burn injury involved 5.7% TBSA, with a wide range from 1 to 47%. The majority of our population involved either small children or intoxicated adults and a total of 50 patients required 92 operations. Severe morbidity, including 4 amputations and 2 mortalities, were seen. The average hospital stay was 14.3 days, ranging from 1 to 52 days. CONCLUSIONS: Recreational outdoor burns were extremely common injuries leading to loss of functional employment and prolonged physical therapy requirements. Small children and intoxicated adults comprised the majority of our study population. The impact and severity of such outdoor fires could be greatly affected by appropriate attention to prevention.

Accidents

Neurochemical organization of the macaque striate cortex: correlation of cytochrome oxidase with Na+K+ATPase, NADPH-diaphorase, nitric oxide synthase, and N-methyl-D-aspartate receptor subunit 1.

Previously, we found that cytochrome oxidase-rich zones in the supragranular layers of the macaque striate cortex had more asymmetric, glutamate-immunoreactive synapses than the surrounding, cytochrome oxidase-poor regions. A major glutamate receptor family is N-methyl-D-aspartate, which is implicated in the stimulation of nitric oxide synthase and in the production of nitric oxide, a gaseous intra- and inter-cellular messenger. To determine if energy-generating and energy-utilizing enzymes bore any spatial relationship with neurochemicals associated with glutamatergic neurotransmission in the monkey visual cortex, serial cortical sections were processed histochemically for cytochrome oxidase and NADPH-diaphorase, and immunohistochemically for sodium/potassium-ATPase, nitric oxide synthase, and N-methyl-D-aspartate receptor subunit 1 protein, respectively. The general patterns were similar among the five neurochemicals, with layers 4C, 6 and supragranular puffs being labelled, although the intensity of labelling differed among them. Monocular impulse blockade with tetrodotoxin for two to four weeks induced a down-regulation of all five neurochemicals not only in deprived layer 4C ocular dominance columns, but also in deprived rows of puffs. Thus, the regulation of all five neurochemicals in the mature visual cortex is activity-dependent. Combined cytochrome oxidase histochemistry and nitric oxide synthase immunohistochemistry in the same sections revealed that double-labelled cells were primarily medium-sized non-pyramidals in various cortical layers. Likewise, those that were double-labelled by N-methyl-D-aspartate receptor subunit 1 immunohistochemistry and nitric oxide synthase immunogold silver staining in the same sections were of the medium-sized non-pyramidal neurons. At the ultrastructural level, combined cytochrome oxidase cytochemistry and postembedding immunogold labelling for nitric oxide synthase showed that immunogold particles for nitric oxide synthase were more heavily concentrated in cytochrome oxidase-rich type C cells. These medium-sized non-pyramidal cells were previously found to be gamma aminobutyric acid-immunoreactive and received both gamma aminobutyric acid- and glutamate-immunoreactive axosomatic synapses. Thus, our results are consistent with an enrichment of excitatory synaptic interactions in metabolically active regions of the primate visual cortex that involves glutamate-related neurochemicals, such as N-methyl-D-aspartate receptors and nitric oxide synthase. These interactions impose a higher energy demand under normal conditions and are down-regulated by retinal impulse blockade.

Animals

Incarcerated adolescents in Washington state. Health services and utilization.

This study describes the health services for incarcerated adolescents in Washington State and their utilization, in 12 juvenile detention facilities statewide, including six state (long-term, postadjudication) and six county (short-term, preadjudication) facilities. Findings differed by facility type, with youth at county facilities having more total visits to emergency rooms and more health care visits per inmate for health problems presenting acutely, such as sexually transmitted disease, pregnancy, urologic problems, and trauma. More were on suicide watch and on psychiatric medication. Health care used by youth at state facilities tended to be for more chronic conditions such as dental, dermatologic, nutritional, and respiratory problems. When utilization was analyzed by size of facility, small facilities had fewer health care visits and fewer nursing hours per inmate. According to our findings, there are at least 14 pregnant adolescents and 2 HIV-infected adolescents incarcerated in this state at any time.

Adolescent

Vinblastine, ifosfamide, gallium nitrate, and filgrastim in platinum- and paclitaxel-resistant ovarian cancer: a phase II study.

The authors performed a phase II trial of the VIG regimen (vinblastine, ifosfamide, and gallium nitrate) in patients who had advanced ovarian cancer who were refractory to cisplatin and/or carboplatin and whose disease had progressed after paclitaxel-based therapy. This was a heavily pretreated population, with five patients having received two to three prior chemotherapy regimens and six patients having received more than six prior chemotherapy regimens, with an average of 21 therapy cycles per patient. Fourteen patients were treated with vinblastine, 0.08 mg/kg intravenously on days 1 and 2; ifosfamide, 900 mg/m2 intravenously on days 1 through 5 with standard mesna uroprotection; and gallium nitrate administered as a continuous intravenous infusion at 225 mg/m2 per 24 hours x 120 hours. Granulocyte colony-stimulating factor (G-CSF) was administered subcutaneously at 5 microg/kg/day beginning on day 7 until day 13. Five of 14 patients achieved a partial response for an overall response rate of 36% (95% confidence interval, 14%-68%). The median response duration was 14 weeks. Toxicity was primarily hematologic, with anemia and leukopenia being most significant. There were no treatment-related deaths. Further evaluation of this regimen in a less heavily pretreated population is warranted.

Aged

Long-term hearing results following vestibular surgery in Meniere's disease.

OBJECTIVES: The purpose of this study is to evaluate the long-term hearing changes following vestibular surgery in patients with Meniere's disease. STUDY DESIGN: This is a retrospective analysis of patients operated on in a tertiary referral center setting. METHODS: Preoperative, postoperative, and 3- to 9-year postoperative audiograms were analyzed in two patient groups. Twenty-one patients underwent posterior fossa vestibular neurectomy (VN) and five, mastoid endolymphatic sac decompression and shunt (ELS). All frequencies, four-frequency pure-tone averages (PTAs), spondee thresholds, and speech recognition scores were compared for operated ear against nonoperated ear of VN subjects. The results were subjected to a covariance analysis. VN and ELS patients whose hearing deteriorated from "serviceable" (PTA < or =70 dB hearing level) and speech recognition > or =30%) to nonserviceable status were compared using nonparametric statistics. RESULTS: Progressive hearing loss beyond the rate of change of the normal contralateral ear was evident in all patients. Serviceable hearing dropped from 81% to 43% of patients an average of 4 years following VN. CONCLUSIONS: VN patients have significant hearing deterioration over time in the operated ear. This finding suggests that continued postoperative medical management is necessary for patients undergoing VN.

Adult

Spontaneous autoimmune diabetes in monoclonal T cell nonobese diabetic mice.

It has been established that insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a CD4+ and CD8+ T cell-dependent autoimmune process directed against the pancreatic beta cells. The precise roles that beta cell-reactive CD8+ and CD4+ T cells play in the disease process, however, remain ill defined. Here we have investigated whether naive beta cell-specific CD8+ and CD4+ T cells can spontaneously accumulate in pancreatic islets, differentiate into effector cells, and destroy beta cells in the absence of other T cell specificities. This was done by introducing Kd- or I-Ag7-restricted beta cell-specific T cell receptor (TCR) transgenes that are highly diabetogenic in NOD mice (8.3- and 4.1-TCR, respectively), into recombination-activating gene (RAG)-2-deficient NOD mice, which cannot rearrange endogenous TCR genes and thus bear monoclonal TCR repertoires. We show that while RAG-2(-/-) 4.1-NOD mice, which only bear beta cell-specific CD4+ T cells, develop diabetes as early and as frequently as RAG-2+ 4.1-NOD mice, RAG-2(-/-) 8.3-NOD mice, which only bear beta cell-specific CD8+ T cells, develop diabetes less frequently and significantly later than RAG-2(+) 8.3-NOD mice. The monoclonal CD8+ T cells of RAG-2(-/-) 8.3-NOD mice mature properly, proliferate vigorously in response to antigenic stimulation in vitro, and can differentiate into beta cell-cytotoxic T cells in vivo, but do not efficiently accumulate in islets in the absence of a CD4+ T cell-derived signal, which can be provided by splenic CD4+ T cells from nontransgenic NOD mice. These results demonstrate that naive beta cell- specific CD8+ and CD4+ T cells can trigger diabetes in the absence of other T or B cell specificities, but suggest that efficient recruitment of naive diabetogenic beta cell-reactive CD8+ T cells to islets requires the assistance of beta cell-reactive CD4+ T cells.

Animals

Radiotherapeutic management of cervical carcinoma that complicates pregnancy.

BACKGROUND: Data regarding radiation therapy for pregnant patients with cervical carcinoma are limited. The goal of this study was to assess the effects of pregnancy on tumor control, survival, and morbidity associated with radiation therapy administered to pregnant patients. METHODS: The authors performed a retrospective case-control analysis of 26 women with cervical carcinoma who were diagnosed during pregnancy and treated primarily with radiation therapy. These cases were matched with 26 controls based on age, histology, stage, treatment, and year of treatment. RESULTS: Patients were treated with external beam radiation (mean dose, 46.7 gray [Gy]) and intracavitary radiation (mean dose, 56.5 Gy to Point A). Two patients with Stage IA2 squamous cell carcinoma treated in the third trimester had a planned delay in treatment of 3 weeks, and both infants had an uncomplicated neonatal course. Seven pregnant patients (2 Stage IB1, 5 Stage IB2) underwent radiation after radical hysterectomy was aborted due to positive regional lymph nodes. Three patients diagnosed during the first trimester were treated with radiation with the fetus in situ, and all had spontaneous abortions 20-24 days after the start of radiation (mean dose, 34 Gy). In all these cases, radiation was interrupted for only 3 days or less. There were no statistically significant differences in recurrence rates or survival between the pregnant group and the controls. Short term toxicity was comparable in pregnant and nonpregnant patients and easily controlled. Long term complications were more common in controls (12% in pregnant patients, 27% in controls), but this difference was not statistically significant. Most complications were likely related to radiation techniques (particularly the predominance of cobalt-60). CONCLUSIONS: Planned delay in treatment should be offered to pregnant patients with early stage squamous cell carcinoma in the late second and early third trimester. Patients diagnosed in the first or second trimester who are not good candidates for planned delay in treatment should be given radiation therapy immediately. It may be necessary to reconsider planned radical hysterectomy for pregnant women with Stage IB2 disease due to the high rate of lymph node positivity found on exploration. For patients with advanced disease, radiation therapy appears to be a safe and effective modality.

Adult