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C Hill

Publications and source records attributed to C Hill.

At least 271 records · Page 15Linked to original sources

Role of radiotherapy and chemotherapy in the risk of second malignant neoplasms after cancer in childhood.

Of a cohort of 634 children treated from 1942 to 1969 at the Gustave Roussy Institute for a first cancer and alive 5 years after treatment, 32 later developed second malignant neoplasms (SMN). A case-control study was performed to determine the relationship between the dose of radiotherapy received on a given anatomical site for the treatment of a first cancer, and the risk of SMN development at the same anatomical site. Another aim of the study was to analyse the effects of the association of radiotherapy with chemotherapy on the risk of SMN. The 32 cases of second malignant neoplasms were individually matched with one to nine patients of the cohort (a total of 162) who did not develop a SMN after a first cancer, matching on age, sex, type of first cancer and follow-up duration. The doses of radiotherapy delivered for the treatment of the first cancer were retrospectively estimated at the 26 anatomical sites of SMN. When the SMN was a leukaemia, the mean active bone-marrow dose was estimated as a weighted mean of the doses received by 20 bone sites. As compared to anatomical sites in children who had not received radiotherapy, the sites which had received 50 Gy or more had a relative risk of SMN of 5.8 (P less than 0.05). When taking into account the dose received at the site of the SMN, neither the number of fractions nor the type of radiations were related to the risk of SMN. Children who had received chemotherapy had a relative risk of SMN of 2.7 (95% CI: 1.2-6.4), adjusted for the dose of radiotherapy, as compared to those who had not. The relative risk of SMN did not vary with the dose nor the duration of the chemotherapy. Dactinomycin was found to increase the relative risk of second soft tissue and bone sarcomas. Cyclophosphamide was found to be less carcinogenic than the other alkylants. The relative risk of SMN was equal to 2.0 (n.s.) after radiotherapy of more than 25 Gy, to 4.4 (n.s.) after chemotherapy, and to 21.4 (P less than 0.01) after the combination of these two treatments modalities, as compared to patients treated by surgery alone. This study suggests that the oncogenic effect of radiations might be increased by chemotherapy, and that the combination of the two treatment modalities might be one of the major factors responsible for overall risk of SMN.

Adolescent↗

Long-term risk of second malignant neoplasm after a cancer in childhood.

The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.

Adolescent↗

Antibiotic treatment and intestinal colonization by Pseudomonas aeruginosa in cancer patients.

To determine whether antibiotic treatment increases the risk of colonization by Pseudomonas aeruginosa, we performed a case-control study comparing antibiotic exposure in cancer patients colonized by P. aeruginosa and in noncolonized controls. Of 88 patients, 76 had been exposed to at least one antibiotic, but colonization was not statistically associated with exposure to any specific antibiotic treatment, administered orally or parenterally, alone or in combination.

Adolescent↗

Localization, cloning, and expression of genetic determinants for bacteriophage resistance (Hsp) from the conjugative plasmid pTR2030.

Genetic determinants for a bacteriophage resistance mechanism (Hsp+) encoded by plasmid pTR2030 (46.2 kilobases [kb]) were localized by mapping an 11.5-kb deletion that accompanied the transition of Lactococcus lactis LMA12-4 transconjugants (M. E. Sanders, P. J. Leonard, W. D. Sing, and T. R. Klaenhammer, Appl. Environ. Microbiol. 52:1001-1007, 1986) from phage resistance to phage sensitivity. The deleted 34.7-kb replicon (pTR2023, Hsp-) retained its conjugative ability, demonstrating that the phage resistance and conjugal transfer determinants were genetically distinct. The Hsp region of pTT2030, which was contained within a 13.6-kb BglII fragment, was cloned into the BamHI site of bacteriophage lambda EMBL3, and Hsp was subcloned into the Escherichia coli-Streptococcus shuttle vector pSA3. The recombinant plasmids pTK6 and pTK9 were recovered in E. coli HB101 and contained a 13.6-kb insert in opposite orientations. L. Lactis MG1363 transformants carrying pTK6 or pTK9 exhibited a significant reduction in plaque size, in addition to a slight reduction in the efficiency of plaquing for both prolate and small isometric phages. Phenotypic reactions observed for the recombinant plasmids suggest that pTR2030-encoded Hsp acts similarly against both prolate and small isometric phages. Tn5 mutagenesis was used to define the region essential for the expression of the Hsp+ phenotype. Any of four insertions within a 3-kb region resulted in the loss of phage resistance, whereas a further 26 insertions outside this locus had no effect on Hsp expression. In vitro deletion analysis confirmed that the 3-kb region contained all the information necessary for the observed resistance.

Bacteriophages↗

The conjugative plasmid pTR2030 encodes two bacteriophage defense mechanisms in lactococci, restriction modification (R+/M+) and abortive infection (Hsp+).

pTR2030 is a conjugative plasmid which encodes resistance to bacteriophage in lactococci by a mechanism that aborts the phage infection (Hsp+). Subcloning and in vivo deletion events showed that two independent mechanisms of resistance are located on a 13.6-kilobase Bg/II fragment cloned in pSA3; one mechanism is responsible for the abortive infection, and the other incodes a restriction modification system. The introduction of pTR2030 or the recombinant plasmid pTK6 resulted in the loss of a resident restriction modification plasmid in Lactococcus lactis NCK202 which was not previously identified.

Bacteriophages↗

Neuropsychological and biomedical assessment of depression-dementia syndromes.

Evaluating the clinical significance of cognitive dysfunction in patients who exhibit signs of both depression and dementia is one of the more formidable challenges in psychiatry. This article reviews cognitive dysfunction associated with depression, the concept of "pseudodementia," and the syndromal phenomenology of coexisting depression and Alzheimer's-type dementia. The state of the art in neuropsychologic, electroencephalographic, metabolic, and neuroradiographic techniques for evaluating dementia and depression syndromes will be discussed, as will implications for the treatment of such patients.

Aged↗

Going in circles.

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Hospital Bed Capacity, 500 and over↗

[Passive smoking and respiratory diseases. Current data].

Smoking is now unanimously recognised as a pathological factor and a major carcinogen. It is estimated that it is responsible for around 10% of the overall mortality in France or more than 50,000 deaths per year and in the United States for around 15% of the overall mortality or 300,000 deaths per year. There has been recent evidence that the risk linked to the inhalation of tobacco smoke does not appear only in active smokers, but also in all subjects who are involuntarily exposed to tobacco smoke. We have here planned a general review of the epidemiological studies which have looked for an association between passive exposure to tobacco and respiratory disease. In children, an increase in symptoms and respiratory infections has been observed, as well as a slowing down in pulmonary growth. In adults the effect of involuntary exposure to tobacco smoke seems above all to be carcinogenic. It is estimated that there is a 25% increase in the risk of bronchial cancer in a non smoker married to a smoker when compared to the risk observed in a non exposed non smoker. Thus the disastrous effect of smoking appears without any threshold.

Adult↗

Asymmetric charge movement and calcium currents in ventricular myocytes of neonatal rat.

1. Calcium and sodium currents and non-linear capacitive currents were recorded from isolated ventricular cells from neonatal rats, using the whole-cell patch-clamp technique, usually with a holding potential of -100 mV. 2. When recording with internal and external solutions designed to suppress virtually all ionic currents except the calcium current, careful subtraction of all linear capacitive and ionic currents revealed that depolarizations elicited a small transient outward current which preceded the inward calcium current. This outward current was discernible just below the threshold potential for the calcium current and increased with larger depolarizations to a maximum for potentials of about +30 mV and above. 3. Elimination of the calcium current revealed that at each potential the transient outward current was accompanied by a roughly equal transient inward current upon repolarization. The properties of these currents indicate that they are non-linear capacitive currents. Best-fit Boltzmann curves of the 'on' charge (integral of the transient outward current) gave values for qmax, V and k of 3.9 nC/microF, -29.3 mV and 15.5 mV with internal Cs+. The maximum 'on' charge is similar to that found with calcium currents (4.3 nC/microF). Similar values were obtained with internal TEA+. 4. Boltzmann fits of conductance vs. voltage for the calcium channel gave mean values of -15.5 and 13.3 mV for V and k (with internal Cs+); the corresponding values for the sodium channel were -49.9 and 5.4 mV. 5. Pre-pulses (20 ms) to -60 mV inactivated 77% of the peak sodium current, but only inactivated about 10% of the peak calcium current and reduced the maximum 'on' charge (moved at potentials positive to -60 mV) by 19%. 6. With a holding potential of -100 mV, 10 microM-nifedipine blocked 89% of the calcium current, but had little effect on the amount of 'on' charge. The 'off' charge appeared to be slower in the presence of nifedipine. 7. These results and consideration of the number of calcium channels and high-affinity binding sites for dihydropyridines (DHP), suggest that a large part of the charge movement may be related to DHP binding sites and involved with gating calcium channels. Comparison with skeletal muscle suggests similarities in the mechanisms involved in excitation-contraction coupling.

Action Potentials↗

Cloning and characterization of the tetracycline resistance determinant of and several promoters from within the conjugative transposon Tn919.

Tn919 is a 15- to 16-kilobase (kb) tetracycline resistance conjugative transposon that was originally isolated from Streptococcus sanguis FC1. The tetracycline resistance determinant (tet) was found on a 4.2-kb HindII fragment by in vitro deletion analysis. This fragment was subcloned to a pWV01 origin capable of directing replication in Escherichia coli, Bacillus subtilis, and Streptococcus lactis, and expression was observed in all three genera. In all cases, expression was weaker when only the 4.2-kb cloned fragment rather than the full transposon was present. The resistance gene is of the streptococcal tetM class and codes for a protein of approximately 70 kilodaltons. The restriction map resembles that of the tetM gene of Tn1545 (P. Martin, P. Trieu-Cuot, and P. Courvalin, Nucleic Acids Res. 14:7047-7058, 1986), which codes for a protein of 72.5 kilodaltons. A number of transposon-derived promoter-bearing fragments were also cloned and sequenced. These closely resemble the consensus sequence of E. coli and B. subtilis promoters. Fusion experiments with a truncated lacZ gene indicate the possibility of an open reading frame for one of the promoters.

Base Sequence↗

Value of semiquantitative cultures of blood drawn through catheter hubs for estimating the risk of catheter tip colonization in cancer patients.

Colonization of central catheter tips has been associated with catheter-related infections. This colonization is defined as the presence of over 15 CFU in a semiquantitative catheter tip culture performed after catheter removal. Using a simple pour-plate technique, we determined the microbial concentrations in samples of blood collected via the hubs of 205 central catheters while they were in position in 179 cancer patients. All catheters were removed within three days of blood collection via the hub and cultured semiquantitatively. We then compared the results for the hub blood cultures and catheter tip cultures. Cultures from 18% of the hub samples and 29% of the tips were positive. When a cutoff limit of 1,000 CFU/ml was used for the blood cultures, the sensitivity was 20% and the specificity was 99% for estimating catheter tip colonization. These values did not seem to be related to the underlying disease, the site of catheter insertion, or the antibiotic treatment administered at catheter removal. We conclude that, if positive, cultures of blood sampled via the catheter hub can be useful in assessing the risk of catheter colonization in cancer patients.

Bacteria↗

Risk factors for candidemia in cancer patients: a case-control study.

Risk factors for candidemia were analyzed in a case-control study of 30 cancer patients with candidemia and 58 controls. In a univariate analysis, previous surgery, neutropenia, central catheterization, chemotherapy, specific antibiotic treatments, and peripheral cultures positive for Candida spp. were associated with a significantly increased risk of candidemia. In a multivariate logistic model, the significant risk factors for candidemia were positive peripheral cultures for Candida spp. (P = 0.02), central catheterization (P = 0.03), and neutropenia (P = 0.05). These results should help to identify cancer patients with a high risk of candidemia, who should be given early systemic antifungal therapy.

Adult↗

[Treatment by drawing lots in a therapeutic trial with a balance distribution of prognostic factors: the minimization method].

In a controlled clinical trial, a more powerful design can be obtained by balancing the treatment groups for the main prognostic factors rather than ignoring these factors in the randomization. The method of random permuted blocks within strata becomes inadequate as the number of prognostic factors increases. Another method known as minimization is described, which balances the marginal distribution of prognostic factors; it was proposed by Taves, and generalized by Pocock and Simon. It avoids the problems arising from an imbalance in a major prognostic factor.

Clinical Trials as Topic↗