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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 217 records · Page 12Linked to original sources
PubMed1996

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

Abdominal Neoplasms↗
PubMed1996

Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13.

Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurode-generative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.

Chromosome Mapping↗
PubMed1996

Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys.

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

Animals↗
PubMed1996

Acquisition of services recommended by a multidisciplinary medical diagnostic team for children under three years of age evaluated for developmental delays.

After multidisciplinary medical diagnostic teams evaluate children with developmental delays, they recommend to parents that they seek specific services, but the team rarely knows which services are obtained. We sought to determine which services pursued by the parents were actually acquired and to determine if there were barriers to the acquisition of services. In a diagnostic clinic located in a teaching hospital in an urban setting, we evaluated 92 children less than 3 years of age mainly from an inner city population. At a family conference, the parents had indicated an interest in pursuing an average of 1.87 +/- 1.34 social services, 1.70 +/- 1.32 educational services, and 3.61 +/- 2.31 medical services recommended by the team. Four months after the family conference, the actual services obtained by families included 38.5% of the social services, 70.87% of the educational services, and 71.36% of the medical services. Significantly fewer social services were obtained than educational and medical services.

Chicago↗
PubMed1996

Hospital closure: Phoenix, Hydra or Titanic?

Very little has been published about the effects of hospital closure in terms of the service, financial or management issues of the process. Attempts through a case-study format to redress the balance and as such represents the reflections of practitioners who have recently undergone the experience of hospital closure and the often neglected issues arising both during and after the process.

Employment↗
PubMed1996

Brain structure and task-specific increase in expression of the gene encoding syntaxin 1B during learning in the rat: a potential molecular marker for learning-induced synaptic plasticity in neural networks.

The mRNAs encoding the synaptic vesicle proteins syntaxin 1B and synapsin I were measured using in situ hybridization in several brain regions--the dentate gyrus, CA3 and CA1 of the hippocampus, the parietal, the motor and prefrontal cortices and the core and shell of the accumbens--of rats that were learning a spatial reference or working memory task on a radial arm maze. The mRNA encoding syntaxin 1B was significantly increased in all hippocampal regions in rats learning the working memory task, whereas it was increased in the prelimbic area of the prefrontal cortex and the shell of the accumbens in rats learning the spatial reference memory task. No change in mRNA encoding syntaxin 1B was observed in the motor and parietal and cortices or the core of the accumbens, and the mRNA encoding synapsin I was not significantly different from that of naive caged controls or rats running the maze for continuous reinforcement in any of the brain structures examined. These results demonstrate that the gene encoding a key member of synaptic vesicle function is up-regulated in a task- and brain-specific manner during learning. They are discussed in terms of the potential role this protein may play in trans-synaptic propagation of plasticity within specific neural networks as a function of the information required in the laying down of different types of memory.

Animals↗
PubMed1996

Validation of the doubly labelled water technique for bumblebees Bombus terrestris (L.)

The doubly labelled water (DLW) technique was validated for the bumblebee Bombus terrestris (L.) using respirometry (RESP) from tethered roundabout flights. We injected small volumes (1 µl) of a mixture containing low concentrations of deuterium and 18O and withdrew 1-2 µl of haemolymph to determine initial 18O concentration. The injected isotopes were equilibrated with the body water pool after 10 min, and high material turnover allowed the analysis of final blood isotope concentrations after 5-7 h. On average (n=16), values measured using the DLW technique exceeded values measured using RESP by 3.1±9.9 %, a difference that was not statistically significant at the 99 % confidence level. The absolute error was 7.4±7.1 % (mean ± s.d.). Isotope dilution spaces of both deuterium and 18O were almost identical with the body water pool. We corrected for isotope fractionation, using a slightly higher value than usual for one of the fractionation factors. The single most important variable to influence DLW results, which could not be measured with the desired accuracy, was the volume of the final body water pool N. An overestimate of final N possibly resulted in the DLW overestimate.

Journal Article↗
PubMed1996

The melatonin hypothesis: electric power and breast cancer.

Breast cancer is a disease of modern life. As societies industrialize, risk increases, yet it is unclear which of the myriad changes coming with industrialization drives this increase. One important hallmark of modern life is the pervasive use of electric power. Electric power produces light at night (LAN) and electric and magnetic fields (EMF), either or both of which may alter pineal function and its primary hormone melatonin, thereby, perhaps increasing the risk of breast cancer. This hypothesis, stated a decade ago, is now receiving considerable experimental and epidemiological attention. The circumstantial case for the hypothesis has three aspects: light effects on melatonin, EMF effects on melatonin, and melatonin effects on breast cancer. The strongest of these aspects is the effects of light on melatonin. It is clear that the normal nocturnal melatonin rise in humans can be suppressed by light of sufficient intensity. The evidence for an effect of melatonin on breast cancer in experimental animals is strong, but the evidence in humans is scant and difficult to gather. The weakest aspect of the circumstantial case is EMF effects on melatonin. Whereas a half dozen independent laboratories have published findings of suppression in animals, there are inconsistencies, and there are no published data on humans. The direct evidence bearing on the hypothesis is sparse but provocative. Two laboratories have published data showing substantial increases in chemically induced breast cancer in rats by a weak AC (alternating current) magnetic field. The epidemiological evidence is very limited but has offered some support as well. An effect of electric power on breast cancer would have profound implications, and this possibility deserves continued investigation.

Animals↗
PubMed1996

Triple therapy and Helicobacter pylori.

Helicobacter pylori is becoming increasingly important as a gastrointestinal pathogen and aetilogical agent in several disease states. This review attempts to clarify the role of Helicobacter pylori and importantly, simplify treatment options.

Amoxicillin↗
PubMed1996

Nonparametric simulation-based statistics for detecting linkage in general pedigrees.

We present here four nonparametric statistics for linkage analysis that test whether pairs of affected relatives share marker alleles more often than expected. These statistics are based on simulating the null distribution of a given statistic conditional on the unaffecteds' marker genotypes. Each statistic uses a different measure of marker sharing: the SimAPM statistic uses the simulation-based affected-pedigree-member measure based on identity-by-state (IBS) sharing. The SimKIN (kinship) measure is 1.0 for identity-by-descent (IBD) sharing, 0.0 for no IBD status sharing, and the kinship coefficient when the IBD status is ambiguous. The simulation-based IBD (SimIBD) statistic uses a recursive algorithm to determine the probability of two affecteds sharing a specific allele IBD. The SimISO statistic is identical to SimIBD, except that it also measures marker similarity between unaffected pairs. We evaluated our statistics on data simulated under different two-locus disease models, comparing our results to those obtained with several other nonparametric statistics. Use of IBD information produces dramatic increases in power over the SimAPM method, which uses only IBS information. The power of our best statistic in most cases meets or exceeds the power of the other nonparametric statistics. Furthermore, our statistics perform comparisons between all affected relative pairs within general pedigrees and are not restricted to sib pairs or nuclear families.

Algorithms↗
PubMed1996

Associations between human leukocyte antigen type and nasopharyngeal carcinoma in Caucasians in the United States.

A genetic component to nasopharyngeal carcinoma (NPC) has been suggested by associations of the malignancy with human leukocyte antigens (HLAs) in Southern Chinese populations, among which NPC is a major cancer. Data from other races are inconclusive. We have investigated associations between NPC and HLA antigens at the HLA-A, B, C, and DQ loci and alleles at the DRB1 locus in a population-based, multicenter investigation in the United States. Data from 82 cases and 140 controls are presented, making this the largest study population analyzing data from Caucasians to date. HLA frequencies from study cases were also compared with external control groups from the 11th International Histocompatibility Workshop and the National Marrow Donor Program. Logistic regression methods were used to investigate the effects of the joint occurrence of multiple HLA types and to assay for differences in HLA-associated risk in different age groups. A meta-analysis was undertaken to compare and summarize our results with previously published findings. The meta-analysis found a protective association with A2 antigen in non-Chinese [odds ratio (OR), 0.63; P < 0.001], a protective association with A11 across all races (OR, 0.54; P < 0.001), and an increased risk associated with B5 in Caucasians (OR, 2.81; P < 0.001). The present study also found independent associations, in a logistic regression model, between NPC and DRB1*1501 (OR, 0.33), DRB1*0405 (OR, 7.57), and Cw3 (OR, 0.42), although these data must be interpreted cautiously due to multiple-testing considerations. Associations were found to be more pronounced in younger patients for A2, A11, A28, B8, and B51.

Adult↗
PubMed1995

Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type.

BACKGROUND: Rates of cancer in children usually are presented in 5-year age groups, despite large variations of incidence within these groups. The purpose of this report is to provide histology-specific incidence rates within single-year age groups, stratified by sex and race, among children. METHODS: Data from the National Cancer Institute's SEER Program were used to calculate incidence rates among children younger than 15 years of age at diagnosis. The SEER population denominator file was modified to allow calculation of rates within single years of age. RESULTS: Large differences in rates within 5-year age groups were found for many histologic types. Retinoblastoma and Wilms' tumor, for instance, had up to eight-fold differences. Substantial differences also were observed for non-Hodgkin's lymphoma, neuroblastoma, Hodgkin's disease, acute lymphoid leukemia, acute myeloid leukemia, and osteosarcoma. In general, rates were higher among males than females, although female rates were often higher among young children. Rates of white children were generally higher than those of black children, especially during the first 5 years of life. Embryonal tumors comprised the majority of neoplasms during the first 2 years of life.

Adolescent↗
PubMed1995

Social and physical anhedonia in relation to cerebral laterality and electrodermal habituation in unmedicated psychotic patients.

The neglect of psychophysiological investigation of social anhedonia, in contrast to physical anhedonia, was addressed by examining relations between electrodermal orienting responses and their lateral asymmetry in unmedicated schizophrenic, bipolar/schizoaffective, and unipolar depressive patients and normal control subjects. In support of relations between social withdrawal and right-hemispheric reactivity, social anhedonia was associated with a predominance of right-hemispheric influences in schizophrenic and bipolar/schizoaffective patients but not in depressive patients. Anhedonia in all but the depressive group was also related to responsiveness, particularly when fast habituators were pooled with nonresponders and compared with moderate and slow habituators. Anhedonia was higher in the more responsive group. This was particularly true of physical anhedonia. The results support associations between both types of anhedonia--social and physical--and psychophysiology, and they also suggest that anhedonia is not a unitary concept.

Acoustic Stimulation↗
PubMed1995

A phase III study of accelerated radiotherapy with and without carboplatin in nonsmall cell lung cancer: an interim toxicity analysis of the first 100 patients.

PURPOSE: In 1989 we initiated a multicenter randomized trial to determine if accelerated radiotherapy with or without concurrent carboplatin improves local control and survival in patients with limited nonsmall cell lung cancer. This interim analysis was performed on the first 100 patients to determine whether the toxicity of the four treatment arms is acceptable. METHODS AND MATERIALS: One hundred patients with limited nonsmall cell lung cancer have been randomized to receive one of four treatments: arm I, radiotherapy 60 Gray (Gy) in 30 fractions in 6 weeks; arm II, accelerated radiotherapy 60 Gy in 30 fractions in 3 weeks; arm III, radiotherapy as in arm I plus carboplatin 350 mg/m2 during weeks 1 and 5 of radiotherapy; arm IV, radiotherapy as in arm II plus carboplatin 350 mg/m2 during week 1. Survival was measured for the group as a whole and treatment-related toxicities in the four arms were compared. RESULTS: The estimated median survival for all 100 patients was 17.1 months with 33% estimated survival at 2 years. The major toxicities were hematologic and esophageal. Patients receiving carboplatin had more neutropenia (p < 0.0001) and thrombocytopenia (p = 0.002) than patients receiving radiotherapy alone, and this was most marked in patients on arm III. Both carboplatin and accelerated radiotherapy separately caused more severe esophagitis when compared to conventional radiotherapy alone (p = 0.011 and p = 0.0017, respectively). Esophagitis was more prolonged in patients having accelerated radiotherapy (p < 0.0001, median duration 3.2 months compared with 1.4 months for patients receiving conventional fractionation). Six patients (23%) treated on arm II have required dilatation of esophageal stricture, one dying with a laryngo-esophageal fistula. CONCLUSION: In patients receiving radiotherapy for unresectable lung cancer, overall treatment time can be halved and carboplatin administered concurrently with increased but acceptable esophageal and hematologic toxicity.

Adult↗
PubMed1995

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care. Australasian Radiation Oncology Lymphoma Group.

PURPOSE: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. METHODS AND MATERIALS: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. RESULTS: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year actuarial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. CONCLUSIONS: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

Adult↗
PubMed1995

Use of a eutectic mixture of local anesthetics for prolonged subcutaneous drug administration.

The efficacy of a eutectic mixture of local anesthetics (EMLA) in alleviating the pain associated with subcutaneous needle insertion for infusion of the iron-chelating agent, deferoxamine, was examined in 12 patients with homozygous beta-thalassemia. As reported by the patient using a 100-mm visual analogue scale, the pain of insertion was rated as significantly less after application of EMLA (mean +/- SD, 1.5 +/- 2.2 mm) than the pain associated with needle insertion without EMLA (34.8 +/- 33.5 mm, P = .005). Subsequently, in a double-blind randomized trial of 10 beta-thalassemia patients, EMLA was significantly better (5.7 +/- 8.2 mm) than placebo (27.0 +/- 22.8 mm, P = .01) in reducing the pain of needle insertion for deferoxamine infusion. No adverse effects were reported with the use of EMLA cream. These results suggest that EMLA may be effective in reducing the pain associated with needle insertion for subcutaneous deferoxamine infusion in beta-thalassemia patients, which may lead to improved compliance with this irritating, prolonged therapy. The safety of EMLA use in these patients, and others receiving regular parenteral therapy, should now be examined.

Anesthetics, Local↗