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Biomedical subjects

C Patterson

Publications and source records attributed to C Patterson.

At least 19 recordsLinked to original sources

Telomere length predicts replicative capacity of human fibroblasts.

When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = -0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue.

Base Sequence

Extraadrenal myelolipoma. A report of two cases.

Two cases of extraadrenal myelolipoma with unusual clinicopathologic features are described. The patient in case 1 had multifocal myelolipomas, involving both the lung and retroperitoneum, that mimicked malignancy, and the patient in case 2 had a single diffuse retroperitoneal myelolipoma without circumscription. Of possible etiologic significance is the fact that both patients were treated with exogenous steroids.

Aged

Effectiveness of a geriatric day hospital.

OBJECTIVE: To determine whether there is a difference in the quality of life between elderly patients managed in a day hospital and those receiving conventional care. DESIGN: Randomized controlled trial; assessment upon entry to study and at 3, 6 and 12 months afterward. SETTING: Geriatrician referral-based secondary care. PATIENTS: A total of 113 consecutively referred elderly patients with deteriorating functional status believed to have rehabilitation potential; 55 were assessed and treated by an interdisciplinary team in a day hospital (treatment group), and 58 were assessed in an inpatient unit or an outpatient clinic or were discharged early with appropriate community services (control group). OUTCOME MEASURES: Barthel Index, Rand Questionnaire, Global Health Question and Geriatric Quality of Life Questionnaire (GQLQ). MAIN RESULTS: Eight study subjects and four control subjects died; the difference was insignificant. Functional status deteriorated over time in the two groups; although the difference was not significant there was less deterioration in the control group. The GQLQ scores indicated no significant difference between the two groups in the ability to perform daily living activities and in the alleviation of symptoms over time but did show a trend favouring the control group. The GQLQ scores did indicate a significant difference in favour of the control group in the effect of treatment on emotions (p = 0.009). CONCLUSION: The care received at the day hospital did not improve functional status or quality of life of elderly patients as compared with the otherwise excellent geriatric outpatient care.

Activities of Daily Living

Iron deficiency anemia in the elderly: the diagnostic process.

OBJECTIVE: To determine the effectiveness of physician probability estimates calculated on the basis of findings from history-taking and physical examination in the diagnosis of iron deficiency anemia in elderly patients. DESIGN: Prospective study. SETTING: Two community hospitals offering secondary and tertiary care. PATIENTS: A total of 259 patients over 65 years of age found to have previously undiagnosed anemia. MEASURES: Physician estimates of the likelihood of iron deficiency before (pretest probability) and after (post-test probability) the laboratory test results were available. The hemogram was available to the physicians when they made their pretest probability estimates. Because the serum ferritin level proved to be the most powerful of the laboratory test results studied, the likelihood ratios associated with the post-test estimates were compared with the ratios associated with the serum ferritin level. MAIN RESULTS: The post-test probability estimates were influenced by the serum ferritin level and the pretest estimates. The post-test estimates derived from the findings obtained through history-taking and physical examination and the laboratory test results (including the serum ferritin level) were slightly less accurate in predicting iron deficiency than the serum ferritin level alone. Nevertheless, a model in which the pretest estimates were used in addition to the serum ferritin level to predict iron deficiency proved to be more powerful than the serum ferritin level alone (p = 0.006). This indicated that the limitations of the post-test estimates were due to a misinterpretation of the serum ferritin level and that the findings from history-taking and physical examination added important diagnostic information. CONCLUSIONS: Physicians must be aware of test properties to provide optimal care to their patients. If test results are properly interpreted, pretest probabilities derived from findings obtained through history-taking and physical examination can add useful information that will lead to more accurate diagnoses.

Aged

Comparative increases of lead and barium with age in human tooth enamel, rib and ulna.

Lead and Ba in postmortem tooth enamel, rib and ulna of six contemporary people (67-96 years; ave. 80) were shown to exhibit similar accumulations with age in the three different types of osseous tissue: Pb/Ca (wt) = 3.0, 5.2, and 3.9 x 10(-5) in rib, ulna, and tooth enamel; and Ba/Ca (wt) = 2.4, 2.4, and 1.8 x 10(-5) in rib, ulna, and tooth enamel, respectively. Mean concentrations of Pb were 11, 19, and 14 micrograms g-1 in rib (ash), ulna (ash), and enamel (dry), respectively. Means for Ba were 8.7, 8.9, and 6.4 micrograms g-1 in rib (ash), ulna (ash), and enamel (dry), respectively. Comparison of Ba in ulna of our 80-year-old subjects with Ba determined by other investigators in bones of younger contemporary populations indicated that Ba accumulates with age at about half the rate of Pb accumulation in bone. Concentrations of Ba in rib, ulna and enamel were positively correlated and similar within an individual, but varied among subjects in proportion to variations in absorptive uptake in portal blood. Barium may diffuse from a blood-dentine source into enamel, where it replaces Ca and accumulates with age. Because of extreme Pb pollution of our 80-year-old subjects and its variation of intake with age, the correlation of Pb in tooth enamel with Pb in bone was more scattered than for Ba. It is shown by means of stable Pb isotopic tracers that: (i) among the three types of osseous tissue, the residence time of Pb is longest in enamel, where it apparently accumulates with age by diffusion with little loss through exchange; and (ii) the residence time of Pb is longer in compact ulna than in trabecular rib, as it accompanies Ca in its osteoblastic transfer from blood to bone and then in its osteoclastic transfer back to blood from bone.

Aged

Natural skeletal levels of lead in Homo sapiens sapiens uncontaminated by technological lead.

Lead, Ba and Ca concentrations were determined in tooth enamel, femur and rib from buried skeletons of PreColumbian Southwest American Indians, 10 subjects who lived 1000 years ago on the Pacific coast at 34 degrees N, and 13 subjects who lived 700 years ago in a desert valley tributary of the Colorado River at 37 degrees N 111 degrees W, both groups living in environments uncontaminated by technological Pb. For the coastal tribe, average Pb/Ca ratios were 1.1 x 10(-7) in enamel, 2.3 x 10(-7) in femur and 4.7 x 10(-7) in rib, while Ba/Ca ratios were 1.2 x 10(-5) in enamel, 32 x 10(-5) in femur and 38 x 10(-5) in rib (wt ratios). For the desert tribe, average Pb/Ca ratios were 4 x 10(-7) in enamel, 11 x 10(-7) in femur and 37 x 10(-7) in rib, while Ba/Ca ratios were 1.1 x 10(-5) in enamel, 7.5 x 10(-5) in femur and 6.2 x 10(-5) in rib. It is shown that biologic levels of Pb and Ba in buried femur and rib at both burial sites and in buried enamel at the Arizona site are obscured by excessive diagenetic additions of Pb and Ba from soil moisture. It is shown that one-third of the Pb in enamel at the Malibu site is biologic, yielding a skeletal Pb/Ca (wt) ratio of 4 x 10(-8). This is equivalent to a mean skeletal concentration of 13 ng Pb g-1 bone ash, and a mean natural body burden of 40 micrograms Pb/70 kg adult Homo sapiens sapiens, uncontaminated by technological Pb. This value is about one-thousandth of the mean body burden of 40 mg industrial Pb/70 kg adult American today, which indicates the probable existence within most Americans of dysfunctions caused by poisoning from chronic, excessive overexposures to industrial Pb.

Adult

Increased incidence of respiratory distress syndrome in babies of hypertensive mothers.

There is controversy over the effect of hypertension in pregnancy on the incidence of neonatal respiratory distress syndrome. We investigated the association between maternal hypertension and the incidence of respiratory distress syndrome in 268 very low birthweight babies of less than 34 weeks' gestation. A lower incidence of respiratory distress syndrome was associated with growth retardation and membrane rupture greater than 24 hours. Maternal hypertension was associated with an increased incidence of respiratory distress syndrome. We used the multiple logistic regression model to control for confounding variables, as the maternal and neonatal factors associated with respiratory distress syndrome were not evenly distributed between the two groups. After adjustment for birth weight, gestational age, growth retardation, and membrane rupture greater than 24 hours, the risk of developing respiratory distress syndrome was significantly greater in babies of hypertensive mothers. Significance was lost when labour before delivery and mode of delivery were taken into account. The increased incidence of respiratory distress syndrome in babies of hypertensive mothers may be due to the absence of labour before delivery because of the greater likelihood of caesarean section.

Cesarean Section

Diagnosis of iron-deficiency anemia in the elderly.

PURPOSE: To determine the value of serum ferritin, mean cell volume, transferrin saturation, and free erythrocyte protoporphyrin in the diagnosis of iron-deficiency anemia in the elderly. PATIENTS AND METHODS: We prospectively studied consecutive eligible and consenting anemic patients over the age of 65 years, who underwent blood tests and bone marrow aspiration. The study consisted of 259 inpatients and outpatients at two community hospitals in whom a complete blood count processed by the hospital laboratory demonstrated previously undiagnosed anemia (men: hemoglobin level less than 12 g/dL; women: hemoglobin level less than 11.0 g/dL). RESULTS: Thirty-six percent of our patients had no demonstrable marrow iron and were classified as being iron-deficient. The serum ferritin was the best test for distinguishing those with iron deficiency from those who were not iron-deficient. No other test added clinically important information. The likelihood ratios associated with the serum ferritin level were as follows: greater than 100 micrograms/L, 0.13; greater than 45 micrograms/L but less than or equal to 100 micrograms/L, 0.46; greater than 18 micrograms/L but less than or equal to 45 micrograms/L, 3.12; and less than or equal to 18 micrograms/L, 41.47. These results indicate that values up to 45 micrograms/L increase the likelihood of iron deficiency, whereas values over 45 micrograms/L decrease the likelihood of iron deficiency. Seventy-two percent of those who were not iron-deficient had serum ferritin values greater than 100 micrograms/L, and in populations with a prevalence of iron deficiency of less than 40%, values of greater than 100 micrograms/L reduce the probability of iron deficiency to under 10%. Fifty-five percent of the iron-deficient patients had serum ferritin values of less than 18 micrograms/L, and in populations with a prevalence of iron deficiency of greater than 20%, values of less than 18 micrograms/L increase the probability of iron deficiency to over 95%.

Aged

Atrial and ventricular arrhythmias in asymptomatic active elderly subjects: correlation with left atrial size and left ventricular mass.

Elderly normal subjects have an increased prevalence of cardiac arrhythmias compared with young and middle-aged subjects. The objective of this study was to test the hypothesis that the incidence and complexity of atrial and ventricular arrhythmias may be related to either left atrial enlargement or to increased left ventricular mass, respectively. From 146 asymptomatic volunteers older than 60 years, 86 subjects were considered to be free of cardiovascular abnormalities and had adequate M-mode echocardiograms and 24-hour ambulatory electrocardiograms. The mean age was 72 +/- 7 years, with a range of 60 to 96 years. There were 37 men and 49 women. During 1415 +/- 73 minutes of ambulatory electrocardiography, the average heart rate was 72 +/- 8 beats/min in men and 76 +/- 6 beats/min in women (p less than 0.05). Atrial arrhythmias were present in 64 subjects (74%); the frequency and complexity of these arrhythmias correlated with left atrial size (p less than 0.01). Ventricular arrhythmias were present in 55 subjects (64%); the frequency and complexity of ventricular arrhythmias did not correlate with left ventricular mass index. These results suggest that left atrial dilatation, a normal development in healthy elderly subjects, plays a significant role in the pathophysiology of the increased incidence of atrial arrhythmias. Increased left ventricular mass, which also occurs normally in the aging heart, is not, on the other hand, associated with an increased frequency and/or complexity of ventricular arrhythmias.

Aged

Intravenous diclofenac sodium. Does its administration before operation suppress postoperative pain?

Intravenous diclofenac sodium was evaluated in a double-blind randomised trial relative to intramuscular diclofenac, intravenous fentanyl, and intramuscular placebo in 160 patients undergoing extraction of impacted lower third molar teeth. The test drug was administered before operation in an attempt to alleviate postoperative pain. A 10-cm visual analogue scale was used to assess pain at 30 minutes and one day after surgery, if the patients stayed overnight. Patients who received intravenous diclofenac had significantly less pain than the other groups 30 minutes after operation. They also had significantly less pain one day after surgery than the placebo or opioid groups, but not less than the intramuscular diclofenac group. Capillary bleeding time, in comparison with placebo, was significantly prolonged after the use of intramuscular diclofenac, and a similar but nonsignificant trend was observed in the intravenous diclofenac group. No problems were encountered with excessive bleeding in any group.

Adolescent

Colorectal cancer in the north and south of Ireland 1950-1984.

STUDY OBJECTIVE: Northern Ireland has the highest standardised mortality ratios for colon cancer in the United Kingdom and the Republic of Ireland has some of the highest mortality rates for cancer in the world. The aim of the study therefore was to investigate trends in colorectal cancer in the north and south of Ireland over the period 1950 to 1984. DESIGN: The study was a cohort analysis of deaths from colorectal cancer for ages 35-74 years by five year age groups, divided by sex. SETTING: This was a population study involving all cases reported to the Registrar General of Northern Ireland and the Eire Vital Statistics and Central Statistical Office during the study period. MEASUREMENTS AND MAIN RESULTS: As in mainland Britain, rectal cancer mortality declined in the north and the south during the study period, but the fall began sooner for males than females. Colon cancer mortality fell in the late 1950s but subsequently rose to its previous high levels. CONCLUSIONS: The observation that there were declines in mortality in the north and south of Ireland in the late 1950s does not support the hypothesis that altered diet due to war rationing in Great Britain and Northern Ireland underlay the fall in British colon cancer mortality after the war. The very high standardised mortality ratios for colon cancer in Northern Ireland highlight a continuing major public health problem in the region.

Adult

Measurement of circulating immune complexes containing IgG, IgM, IgA and IgE by flow cytometry: correlation with disease activity in patients with systemic lupus erythematosus.

The immunoglobulin (Ig) class of the antibody component of circulating immune complexes (IC) may be an important determinant of their pathogenicity. This study reports the development of a fluorometric immunoassay, using Raji cells as solid phase component and detection by flow cytometry, for the measurement of IC containing IgG, IgM, IgA and IgE. Analytic specificity of the method was established and diagnostic sensitivity determined in groups of patients with various disorders. In a detailed study of 44 patients with systemic lupus erythematosus (SLE), elevated levels of IC were observed in the majority of patients, the prevalence of the respective Ig subclasses within the patient group being IgG-IC (93%); IgM-IC (77%); IgA-IC (59%); IgE-IC (52%). Raised levels of IC (of all classes) correlated with disease activity. Longitudinal study of a patient with acute cerebral SLE revealed elevated IC levels of all four Ig classes at presentation which fell during treatment, coincident with normalization of complement values. The biological consequences of IC of various Ig subclasses is discussed with particular reference to a possible mechanism of IgE-IC mediated tissue damage.

Adult

A new dwarfing syndrome with extreme shortening of humeri and severe coxa vara.

A previously undescribed form of short-limbed dwarfism is reported in an 86-year-old man. All the long bones were shorter than normal, with extreme shortening of the humeri. Other features included dysplastic humeral heads, coxa vara with dysplasia of the femoral heads and acetabula, platybasia, and small vertebral bodies. In all other respects, including intelligence, the patient was normal for his age.

Aged