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Biomedical subjects

R Gelman

Publications and source records attributed to R Gelman.

At least 19 recordsLinked to original sources

Lymphocyte subsets in healthy children during the first 5 years of life.

OBJECTIVE: To assess whether relative and absolute values of CD4 and CD8 lymphocytes and CD4/CD8 ratio change in relation to age, and to estimate the fifth and 95th percentiles for these values in children of various ages. PATIENTS AND METHODS: Phenotypic analysis of lymphocyte subsets was performed on blood samples from 208 healthy children, aged 1 through 59 months, using standard flow cytometric techniques. RESULTS: Regression analysis demonstrated that CD4 and CD8 lymphocyte counts declined significantly with advancing age (P less than .000001 and P = .03, respectively). Since CD4 and CD8 counts depend on total lymphocyte count, the percentage of total lymphocytes of each phenotype was also analyzed and demonstrated that the CD4 percentage was highly age dependent (P less than .000001). The CD8 percentage increased with age (P = .0001) but not as much as the CD4 percentage decreased. Median CD4 counts (fifth and 95th percentiles) for children 2 through 3, 4 through 8, 12 through 23, and 24 through 59 months of age were 2.83 (1.46 to 5.11), 2.95 (1.69 to 4.61), 2.07 (1.02 to 3.60), and 1.80 (0.90 to 2.86) x 10(9)/L, respectively. CONCLUSION: Healthy children's CD4 lymphocyte counts are considerably higher than previously established adult values. These data demonstrate that age is an important consideration in interpretation of lymphocyte subsets in children. This may be especially relevant in children who are infected with the human immunodeficiency virus, where CD4 lymphocyte values play a central role in monitoring disease progression and determining thresholds for medical interventions.

CD4-CD8 Ratio

Preverbal and verbal counting and computation.

We describe the preverbal system of counting and arithmetic reasoning revealed by experiments on numerical representations in animals. In this system, numerosities are represented by magnitudes, which are rapidly but inaccurately generated by the Meck and Church (1983) preverbal counting mechanism. We suggest the following. (1) The preverbal counting mechanism is the source of the implicit principles that guide the acquisition of verbal counting. (2) The preverbal system of arithmetic computation provides the framework for the assimilation of the verbal system. (3) Learning to count involves, in part, learning a mapping from the preverbal numerical magnitudes to the verbal and written number symbols and the inverse mappings from these symbols to the preverbal magnitudes. (4) Subitizing is the use of the preverbal counting process and the mapping from the resulting magnitudes to number words in order to generate rapidly the number words for small numerosities. (5) The retrieval of the number facts, which plays a central role in verbal computation, is mediated via the inverse mappings from verbal and written numbers to the preverbal magnitudes and the use of these magnitudes to find the appropriate cells in tabular arrangements of the answers. (6) This model of the fact retrieval process accounts for the salient features of the reaction time differences and error patterns revealed by experiments on mental arithmetic. (7) The application of verbal and written computational algorithms goes on in parallel with, and is to some extent guided by, preverbal computations, both in the child and in the adult.

Animals

Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria.

Although the categorization of proliferative breast lesions provides valuable information regarding subsequent risk of breast cancer, the ability of pathologists to classify such lesions in a reproducible fashion has not been adequately evaluated. To assess further interobserver reproducibility in the categorization of proliferative breast lesions, six pathologists each reviewed 24 proliferative ductal lesions and classified them as either usual hyperplasia (H), atypical hyperplasia (AH), or carcinoma in situ (CIS). Before evaluation of the study slides, all the participants were instructed to use the diagnostic criteria of Page and co-workers and were provided with both a written summary of these criteria and a set of teaching slides with representative examples of each type of lesion. Complete agreement among all six pathologists was seen in 14 cases (58%); five or more agreed in 17 cases (71%); and four or more arrived at the same diagnosis in 22 cases (92%). No pathologist consistently rendered more "benign" or "malignant" diagnoses than any other. After assigning numerical values for each diagnostic category (H = 1, AH = 2, CIS = 3), the scores for the group of 24 cases did not differ significantly by pathologist (p = 0.68; average score range, 1.7-2.0). Our results indicate that with the use of standardized criteria, interobserver concordance in the diagnosis of proliferative ductal breast lesions can be obtained in the majority of cases.

Breast

Normal uptake in a gravid uterus on Tc-99m DTPA imaging.

A 17-year-old female kidney transplant patient was admitted to the hospital with a fever and right lower quadrant pain. Although she was 14 weeks' pregnant, renal DTPA imaging was performed because graft rejection was suspected. The study revealed fetal uptake of DTPA medial to the transplanted kidney. This has not been previously reported. Uptake in a normal uterus has been described using Tc-99m pertechnetate, Tc-99m glucoheptonate, and Tc-99m MDP. It is essential to recognize uptake in the gravid uterus and to differentiate it from uptake secondary to a pathologic entity.

Adolescent

Recurrence in the breast following conservative surgery and radiation therapy for early-stage breast cancer.

This report summarizes the experience of the Joint Center for Radiation Therapy (JCRT) in treating patients with clinical stage I and II breast cancer with conservative surgery and radiation therapy. The study population consisted of 1396 patients treated between 1968 and 1985. All patients underwent a gross excision of the tumor and received breast irradiation (with or without nodal irradiation) including a "boost" to bring the primary tumor site to a total dose of at least 60 Gy. The method of treatment evolved over the study-time period. During the interval from 1968 to 1982, patients typically underwent a limited gross excision of the tumor without regard to the microscopic margins of resection. During the period 1983 to 1985, film-screen mammography, inking of specimen margins, and reexcisions for inevaluable or involved margins were more commonly performed. With a median follow-up of 80 months, the 5-year crude rate of failure in the breast (as the first site of failure) was 8% (106/1396) and the crude rate of regional nodal/distant failure (as the first site of failure) was 16% (228/1396). The time-course of failures in the breast was protracted, occurring at a fairly constant rate over the first 7 years after treatment, but still seen beyond that point. Most recurrences in the breast (75%) developed at or near the original tumor site. The most important risk factor for developing a breast recurrence was the presence of an extensive intraductal component in the tumor. The cosmetic results following treatment were excellent or good in the majority of patients (87%) and were most adversely affected by extensive surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms

The use of radionuclide imaging in the evaluation of suspected biliary damage during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy offers a reliable and effective alternative to the standard operative cholecystectomy with reduced morbidity and patient recovery time. We report three cases in which radionuclide hepatobiliary imaging was utilized to evaluate the integrity of the extrahepatic biliary ducts following suspected biliary damage during the procedure, documenting bile leakage in two of the patients.

Adult

Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study.

Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with mitolactol, doxorubicin, vincristine (DAV), tamoxifen, and fluoxymesterone (DAVTH). Nine patients were canceled, and 114 were ineligible (half because of concomitant diseases). Among the 501 eligible patients, the overall response rate was 54% (14% complete response and 5% not assessable). The median time to treatment failure (TTF) was 9.0 months, and the median survival was 20.9 months. Multivariate models were fit on a randomly chosen half of the eligible cases and then verified on the other half. About half of the variables that were significant in the models remained significant in the verification data set. In the verification data set the variables that remained significantly associated with lower probability of response were three or more organ sites of disease and lack of nodal metastases; the variables associated with a significantly shorter TTF were liver metastases, estrogen receptor (ER)-negativity, and prior adjuvant therapy. The variables associated with significantly shorter survival were liver metastases, ER negativity, three or more organ sites of disease, and prior adjuvant chemotherapy. None of the variables in the data set had a significant influence on toxicity. The 125 patients aged over 65 years did not have worse toxicity or worse prognosis than younger patients. Ineligible patients had significantly less response but virtually identical TTF curves, survival curves, and toxicities. Therefore, patient discriminants are of paramount importance in predicting the outcome of treatment. Many of the current criteria for eligibility for entry on study may not be justified.

Adenocarcinoma

Diaphragmatic rupture due to blunt trauma: sensitivity of plain chest radiographs.

Preoperative diagnosis of diaphragmatic rupture caused by blunt injury is often difficult because of serious concurrent injuries, a lack of specific clinical signs, and simultaneous lung disease that may mask or mimic the diagnosis radiologically. Previous reports have suggested that a preoperative diagnosis is established on the basis of chest radiographs in only one third of patients. In order to assess the value of chest radiographs and other imaging techniques in diagnosing traumatic rupture of the diaphragm, we retrospectively reviewed all preoperative diagnostic imaging performed in 50 patients with surgically proved hemidiaphragmatic rupture due to blunt trauma. Chest radiographs were diagnostic in 20 (46%) of 44 patients with left-sided rupture and were considered suspicious enough to warrant further diagnostic studies in an additional eight patients (18%). Five patients with initially normal findings on chest radiographs had diagnostic findings on delayed chest radiographs. Chest radiographs were strongly suggestive in only one (17%) of six patients with right-sided hemidiaphragmatic rupture. CT was diagnostic for diaphragmatic rupture in only one (14%) of seven instances in which it was performed. MR was diagnostic in both patients in whom it was performed. Our experience indicates that chest radiographs obtained at admission and repeated soon after are more valuable in suggesting the diagnosis of traumatic rupture of the diaphragm than previously reported, particularly in the more frequent, left-sided injuries. This increased sensitivity may be due to a greater level of suspicion maintained in a trauma referral center in which this injury is not uncommon.

Adolescent

Nuclear binding of the estrogen receptor: a potential predictor for hormone response in metastatic breast cancer.

We have previously described an in vitro immunohistochemical test employing anti-receptor antibodies, for demonstrating the nuclear binding characteristics of estrogen receptors (ER) in breast carcinomas. Based on a retrospective analysis of twenty-five patients with estrogen receptor-positive (ER+) breast cancer who were treated with hormone therapy and whose clinical responses were evaluable, we were able to demonstrate that this test may be valuable to predict which, among the ER+ tumors (whether or not they are progesterone receptor positive, PR+), are likely to respond to hormone therapy and which may fail. While tumors in which ER exhibited abnormalities in nuclear binding behavior (ligand-independent nuclear binding or no nuclear binding) failed hormone therapy (16 out of 19 patients), those in which nuclear binding of ER appeared normal (ligand-dependent) in the in vitro test, responded to hormone therapy (5/6 patients). While our previous report dealt with the procedural details, specificity of the reagents, and the design of the study, this report addresses the clinical aspects of this study and response correlation.

Biomarkers, Tumor

Numerical abstraction by human infants.

Across several experiments, 6- to 8-month-old human infants were found to detect numerical correspondences between sets of entities presented in different sensory modalities and bearing no natural relation to one another. At the basis of this ability, we argue, is a sensitivity to numerosity, an abstract property of collections of objects and events. Our findings provide evidence that the emergence of the earliest numerical abilities does not depend upon the development of language or complex actions, or upon cultural experience with number.

Attention

Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy.

The identification of factors associated with breast recurrence following conservative surgery (CS) and radiation therapy (RT) is of potential use in refining patient selection criteria and treatment technique. In an attempt to define such factors we examined the relationship between various clinical, pathologic and treatment characteristics and the likelihood of breast recurrence in 783 patients with clinical stage I or II breast cancer treated between July 1968 and December 1982. Treatment consisted of complete gross excision of the primary tumor and RT to a total dose of at least 60 Gy to the primary site. During this period, pre-treatment mammograms and detailed histologic assessment of the margins of resection were not routinely performed. Median follow-up for surviving patients was 80 months. Thirteen patients (1.6%) were lost to follow-up. Ninety-one patients (12%) have developed a breast recurrence, corresponding to 5- and 10-year actuarial rates of 10 and 18%, respectively. The major feature associated with breast recurrence was the presence of an "extensive intraductal component" (EIC+). An EIC+ tumor was seen in 28% of evaluable cases with infiltrating ductal carcinoma and accounted for 60% of breast recurrences. Forty-three of 166 patients (26%) with EIC+ tumors developed a breast recurrence compared with 29 of 418 patients (7%) without an EIC (EIC-) (p = 0.0001). The 5-year actuarial rates of breast relapse were 24 and 6%, respectively (p = 0.0001). Very young age (defined as 34 years of age or younger) was also a significant factor associated with the risk of breast recurrence. Very young patients comprised 8% of the patient population and accounted for 16% of breast recurrences. Fifteen of 61 very young patients (25%) developed a breast recurrence compared with 76 of 722 older patients (11%) (p = 0.001). The corresponding 5-year actuarial rates of breast recurrence were 21 and 9% (p = 0.005). None of the other clinical or pathological factors examined by univariate analysis were significantly correlated with recurrence in the breast. A multivariate model of site of first failure (polychotomous logistic regression) also showed that EIC+ tumors and very young age were the main factors associated with a high relative risk of breast recurrence. We conclude that EIC+ tumors and very young age are associated with a high risk of breast recurrence for patients treated with limited excision prior to RT.

Actuarial Analysis

Genetics of survival in mice: subregions of the major histocompatibility complex.

In this study of murine survival, 422 F1 hybrids between DBA/2J (D2) female mice and C57BL/10 (B10) background H-2 congenic male mice (11 strains), 88 F1 hybrids between B10 female mice and B10 background H-2 congenic male mice (3 strains), and 532 control mice from the 11 parental B10 background H-2 congenic mice were bred over a period of 2 yr. Toward the end of the breeding period there was documentation of Sendai infection in the mouse rooms. All analyses were done separately for the two sexes. Although it did not appear that an unusually high number of mice died during the time the colony was infected with Sendai, there was a highly significant tendency for mice who were younger at the time of the Sendai infection to have shorter survival than mice who were older at that time point. The effect of birth date on survival was approximately as significant as the effect of strain on survival. Hence all analyses of genetic effects on survival were either done within subsets of mice born in the same quarter of a particular year or else included date of birth variables in survival models. Of the 18 possible comparisons of pairs of strains which overlapped in birth dates and differed only in the D end of H-2, five were associated with highly significant survival differences. Of the 11 pairs of strains which overlapped in birth date and differed only in the K end of H-2, none was associated with significant survival differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast.

Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.

Breast