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A phase II survival comparison of patients with adenocarcinoma of the pancreas treated with 5-fluorouracil and calcium leucovorin versus a matched tumor registry control population.

Carcinoma of the pancreas is a virulent malignancy. We performed a Phase II survival study by treating 30 patients with pancreatic cancer with leucovorin, 200 mg/m2 x 5 days immediately followed by 5-fluorouracil, 370 mg/m2 every 4 weeks. We examined the survival of our 30 study patients with patients drawn from the Manitoba Tumor Registry, matched for important prognostic criteria. Classical response rates were also evaluated in those patients who had measurable tumors. The response rate was 13% with two complete remissions and one partial remission, with 40 patients (7.8%) demonstrating stable disease for 2 months, and 39% of patients demonstrating progressive disease while on treatment. The mean survival of the Phase II-treated group was 16 weeks, compared to 12 weeks in the matched controls, which indicated an increase in survival of 30%. This was significant at the p = .001 level. Toxicity was not as great as expected. This trial demonstrates that there may be marginal survival benefit with 5FU leucovorin in pancreatic cancer, but more profound prolongation needs to be seen with chemotherapy regimens before instituting randomized trials.

Adenocarcinoma↗

[Patellar malposition, its incidence in patellar chondropathy and in a control population].

Patellar disequilibrium consists of either external malpositioning of the patella (EMP) or external hyperpression (EHP), which are clearly visible on a 30degrees axial radiograph of the knee. Does this disequilibrium play a role in the development of patellar chondropathy? The authors have based their comparisons on a series of 40 subjects more than 60 years of age (average age: 68 years) who were free from pain and arthrosis of the knee. In this group they found 2 cases of EMP (5 percent) and 3 of EHP (7.5 percent). In their series of cases of patellar chondropathy (43 cases) there were, after correction for the cases with a double etiology, 8.5 cases of EMP (20 percent) and 7 of EHP (16 percent). The differences between these figures and those for the control series are statistically significant for the number of cases of EMP (P less than 0.05), but not for the number of cases of EHP, the etiological role of which is probable but for which proof would require a larger series of patients. From this work the following findings emerge: (1) The frequency of latent patellofemoral arthrosis in the aged control subjects with knee problems. 7 cases out of 47, or 12.5 percent. (2) The frequency of patellar chondropathy apparently associated with the two etiological factors: out of 43 patients, 22 suffered from patellar disequilibrium (10 EMP and 12 EHP) but in 13 cases there was another associated possible cause of deterioration: traumatism or stress on the knee associated with work or sport. This methodological difficulty is discussed and resolved empirically. The importance of patellar disequilibrium in the development of degenerative patellofemoral affections derives not from the etiological importance but from the fact that they represent the only factor for which therapy may be given: elective internal rehabilitation or surgery (section of the external wing of the patella or transposition of the anterior tuberosity of the tibia).

Aged↗

Rapid genotyping of transforming growth factor beta1 gene polymorphisms in a UK Caucasoid control population using the polymerase chain reaction and sequence-specific primers.

Transforming growth factor (TGF) beta1 is a growth factor which has multiple functions including the promotion of matrix deposition during wound healing and scar formation. Gene polymorphisms within or close to the 5' region of TGFbeta1 have been identified; three in the upstream region, one in the non-translated region, two in the signal peptide sequence and one in a region of the gene coding for the precursor protein. We have developed a method using 14 polymerase chain reaction-sequence-specific primer reactions to characterise six of these polymorphisms. In the upstream region, both forward and reverse allele-specific primers were used to demonstrate the cis/trans orientation of alleles at adjacent polymorphisms (haplotypes). We report the allele and genotype frequencies of TGFbeta1 genes in two sets of UK Caucasoid control subjects.

DNA Primers↗

Contribution of body composition to nutritional assessment at hospital admission in 995 patients: a controlled population study.

Body weight, weight changes and BMI are easily obtainable indicators of nutritional status, but they do not provide information on the amount of fat-free and fat masses. The purpose of the present study was to determine if fat-free mass (FFM) and fat mass were depleted in patients with normal BMI or serum albumin at hospital admission. A group of 995 consecutive patients were evaluated for malnutrition by BMI, serum albumin, and 50 kHz bioelectrical impedance analysis and compared with 995 healthy adults, matched for age and height, and then compared with FFM and fat mass percentiles previously determined in 5225 healthy adults. A BMI of <or=20 kg/m2 was noted in 17.3 % of patients and serum albumin of <or=35 g/l was found in 14.9 % of patients. In contrast, 31 % of all patients were below the tenth percentile for FFM, compared with 10.1 % of controls (chi2, P=0.0001), while 73 % of patients with BMI <or=20 kg/m2 and 31 % of patients with BMI 20-24.9 kg/m2 fell below the tenth percentile for FFM. Furthermore, the FFM was lower in patients than controls and the differences with age in FFM (lower) and fat mass (higher) were greater in patients than in controls. BMI and albumin significantly underestimated the prevalence of malnutrition in patients at hospital admission compared with body composition measurements. Optimal nutritional assessment should therefore include objective measurement of FFM and fat mass.

Adipose Tissue↗

Prevalence of malnutrition in 1760 patients at hospital admission: a controlled population study of body composition.

OBJECTIVE: Malnutrition, defined as low or excessive body weight, is associated with increased hospital length of stay and cost of care. The purpose of this study was to determine if fat-free mass (FFM) and body fat (BF) differed between patients at hospital admission in Geneva and Berlin and healthy volunteers, and if there is a difference in the prevalence of low FFM (percentile P<10) and high BF (percentile P>90) between patients and volunteers. METHODS: In total, 1760 patients (Geneva: 525 men, 470 women; Berlin: 397 men, 368 women) were evaluated for malnutrition by BMI, serum albumin, and FFM and BF, determined by bioelectrical impedance analysis (BIA), and compared to 1760 healthy volunteers matched for age and height, and further compared to FFM and BF percentiles, previously determined in 5225 healthy adults. RESULTS: The prevalence of FFM P<10 was greater in patients than controls. The prevalence of albumin<35 g/l (14.9% and 11.2% in Geneva and Berlin patients, respectively) and BMI<20.0 kg/m(2) was lower than the prevalence of low FFM (31.3% and 17.3%, respectively). The prevalence of high BF in Berlin patients was three-fold the prevalence of volunteers. Twelve and twenty percent of Geneva and Berlin patients, respectively, with normal BMI had high BF, compared to 4% of volunteers. CONCLUSIONS: Geneva and Berlin patients had lower FFM and higher BF than age-and height-matched volunteers and a higher prevalence of low FFM and high BF. Serum albumin and BMI underestimated the prevalence of malnutrition in patients at hospital admission. Body composition measurements identified patients with low FFM and low or high BF reserves.

Adipose Tissue↗

Diagnosis, clinical staging, and treatment of breast cancer: a retrospective multiyear study of a large controlled population.

This study compares diagnosis, staging, and treatment of newly diagnosed breast cancer cases over a several-year period. The study design was a retrospective, multiyear comparison between new breast cancer cases diagnosed in 1995 (n = 827) and 1997 (n = 815). Cases were identified through claims data, and medical record abstraction was used to verify each case and to identify clinical staging and type of treatment. All medical records were reviewed by one physician to maximize internal reliability. Both cohorts were predominantly 40 and older, white, married, and postmenopausal. The latter cohort (1997) had a higher proportion of women aged 70 to 79 and a lower proportion of women aged 40 to 49. In both cohorts, women age 40 and older were likely to be diagnosed with breast cancer at the time of mammographic screening, while women younger than 40 were more likely to be diagnosed by clinical breast examination. In logistic regression analyses, controlling for confounding factors such as age, undergoing mammographic screening increased the likelihood of having a low cancer stage at diagnosis by more than three and a half times. Mammographic screening was statistically significantly positively associated with having eligibility for breast-conserving treatment (BCT); however, although an increase in BCT eligibility was observed, actual use of BCT did not change. Mammography leads to a lower clinical stage as well as a greater likelihood of BCT eligibility at time of breast cancer diagnosis, but may not have a substantial effect on treatment choice (lumpectomy vs. mastectomy). Between 1995 and 1997, a trend was observed toward downstaging of disease at diagnosis; further research is warranted to observe whether this trend continues over time.

Adult↗

Anterior pituitary cell population control: basal cell turnover and the effects of adrenalectomy and dexamethasone treatment.

We have used an extremely accurate, dedicated, real time computerized image analysis system to facilitate the manual quantification of changes in the prevalence of mitotic figures and apoptotic bodies in male rat pituitary following surgical adrenalectomy and, 14 days later, dexamethasone treatment. Under basal conditions, the prevalence of mitotic figures and apoptotic bodies was 0.066+/-0.016% and 0.030+/-0.012% (mean+/-SE) respectively. Dexamethasone treatment reduced the prevalence of mitotic figures and, in adrenalectomized animals, produced a highly significant and reproducible burst of apoptotic activity that peaked 48 h after the beginning of treatment (0.261+/-0.022%) before falling sharply to control levels within a further 8 h. Two weeks after the start of dexamethasone treatment, total pituitary cell numbers continued to decline. The rate of accumulation of mitotic figures in vivo after colchicine treatment indicates that mitosis is histologically overt in 2 microm thick hematoxylin and eosin stained sections under the light microscope for around 80 min; that apoptosis--identified as classical apoptotic bodies--is overt for 44 min and that, on average, a young, adult, male rat anterior pituitary cell either dies or divides as frequently as once every 60-70 days. These data show that transient and apparently trivial fluctuations in the prevalence of apoptotic and mitotic events have a profound effect on pituitary cell population dynamics, and demonstrate that dexamethasone treatment of adrenalectomized rats produces a decline in total anterior pituitary cell numbers that continues for at least 2 weeks after the start of glucocorticoid treatment.

Adrenalectomy↗

On the dynamics of flying insects populations controlled by large scale information.

We present a diffusion model adapted to an operational control of flying insects. The operational objective entails working with non-homogeneous regions and the corresponding non-uniform diffusion tensors. It the becomes necessary to study the problem of scale in order to justify the diffusion equation. We show that in typical cases, the spatial resolution must be coarser than 20 m and we have specified the appropriated time scales. We propose a method for computing the tensors at the given resolution, in relation to the landscape and the insects' species and a method for the numerical solution of the equations and present two applications.

Animals↗

A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls.

BACKGROUND: Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS: The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS: Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS: Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

Adult↗

Analyses of chromium and nickel in human pulmonary tissue. Investigations in lung cancer patients and a control population under special consideration of medical expertise aspects.

After inhalative occupational exposure to certain compounds containing nickel and chromium (mostly over many years), an accumulation of these metals may occur in the lung tissue. This is of particular importance, both from a toxicological point of view and with regard to expert reports, since certain nickel and chromium compounds may induce lung cancers. In the context of this study, samples of pulmonary tissue from 34 deceased persons from the Bergen area (Norway) were analysed by atomic absorption spectrometry with regard to their content of chromium and nickel. The deceased comprised 21 men and 13 women. In 15 cases, death resulted from lung cancer; in the other 19 deceased, there was no indication of a malignant disease of the airways. The concentrations of nickel found in the lung tissue do not differ between patients with lung cancer and patients with healthy lungs. On the other hand, the concentration of chromium in the pulmonary tissue in the patients who had died of lung cancer and who had all been inhalative smokers, are higher (statistically significant) than in the nonsmokers or in those with healthy lungs. An accumulation of these two metals in the tumor matrix could not be detected. Both the average nickel and the average chromium concentrations were higher in the persons who had probably been exposed occupationally. Considering the present state of scientific knowledge, the aspects relevant to expert reports which result from the analyses of metals in the pulmonary tissue are discussed.

Adult↗