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Biomedical subjects

D J Tollerud

Publications and source records attributed to D J Tollerud.

At least 19 recordsLinked to original sources

Elevated soluble interleukin-2 receptors in young healthy cigarette smokers: lack of association with atopy or airways hyperresponsiveness.

To study the relationship of atopy and nonspecific airways hyperresponsiveness to circulating levels of soluble interleukin-2 receptors (sIL-2R), we measured serum sIL-2R concentrations in 40 young, healthy smokers and non-smokers. Levels of sIL-2R were significantly higher in current smokers than in nonsmokers (median sIL-2R levels 605 vs. 398 U/ml, respectively; p less than 0.05). Serum sIL-2R levels were not related to nonspecific airways hyperresponsiveness to methacholine, allergy skin test reactivity, doctor-diagnosed asthma or hay fever, or respiratory symptoms of wheeze. Among current smokers, a trend toward higher sIL-2R levels (not statistically significant) was observed among subjects reporting symptoms of phlegm production. The increase in sIL-2R levels associated with cigarette smoking was similar in magnitude to that reported for immune-mediated conditions such as collagen vascular diseases and eczema. These data confirm that cigarette smoking is an important determinant of sIL-2R level, even among young healthy subjects. This effect does not appear to be related to atopic status or bronchial responsiveness. Among cigarette smokers, sIL-2R level may be related to the presence of conditions associated with phlegm production.

Humans

Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on cell subset proportions and fluorescence intensity.

The effect of cryopreservation and long-term liquid nitrogen storage on peripheral blood mononuclear cell (PBMC) subsets was prospectively analyzed using monoclonal antibodies and flow cytometry. Brief cryopreservation did not significantly alter the proportion of positively stained cells for CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells. A small but statistically significant increase in the proportion of positive cells was observed for HLA-DR+ and HLe-1+ cells. Brief cryopreservation was associated with a decrease in the mean fluorescence intensity (MFI) values for CD3+, CD4+, and CD8+ cells; an increase in MFI values for CD14+ and HLA-DR+ cells; and no change for CD16+, CD19+, and HLe-1+ cells. There was no significant change in the proportion of CD3+, CD4+, or CD16+ cells during 20 months of storage in liquid nitrogen. Small but statistically significant decreases in the proportion of CD8+ and CD19+ cells were observed over the same interval, and the proportion of CD14+ cells (monocytes) was highly variable. Chronologic changes in fluorescence intensity during long-term storage were observed for all cell subsets except CD16+ and CD19+ cells. Cryopreservation is a valuable technique for long-term storage of viable cells. For many laboratory applications, the small changes noted in the present study will have no practical importance. However, for clinical and epidemiological investigations encompassing large numbers of samples, statistical techniques to adjust for small changes during storage should be considered.

Antigens, CD

T cell subsets in healthy black smokers and nonsmokers. Evidence for ethnic group as an important response modifier.

The influence of cigarette smoking on T cell subsets has been studied in white subjects, but comparable data are not available for blacks. We analyzed peripheral blood mononuclear cell subsets in a population-based, stratified, random sample of healthy black adults using monoclonal antibodies and flow cytometry. The study population consisted of 94 men and 79 women, including 73 smokers (CS) and 100 nonsmokers (NS). Cigarette smoking was associated with a significant elevation in leukocyte (WBC) count (CS 7,270 +/- 230 cells/mm3 versus NS 6,260 +/- 160 cells/mm3; p = 0.001), although WBC counts for both groups were substantially lower than those reported for white smokers and nonsmokers. Smokers had a significantly lower proportion of CD4+ cells than nonsmokers (CS 55.4 +/- 0.9% versus NS 58.7 +/- 0.9; p = 0.01), adjusting for age and gender. No significant smoking-related changes were observed for CD8+ cells, the CD4/CD8 ratio, or total T cells (CD3+), monocytes (CD14+), or natural killer cells (CD16+). Among black smokers, a significant dose-related decrease in CD4+ cells was observed as the number of cigarettes smoked per day increased. Among black exsmokers, the level of WBC and CD4+ cells returned to the level observed in never smokers within 2 to 5 yr after smoking cessation. These results contrast sharply with the previously reported increase in CD4+ cells and decrease in natural killer cells associated with cigarette smoking in whites. The data suggest that the immunologic effects of cigarette smoking may be significantly modified by ethnic characteristics.

Adult

Asthma, hay fever, and phlegm production associated with distinct patterns of allergy skin test reactivity, eosinophilia, and serum IgE levels. The Normative Aging Study.

We investigated the relationship of three phenotypic markers of atopy (allergy skin test reactivity, serum IgE level, and eosinophilia) to the prevalence of respiratory symptoms in 1,071 middle-aged and older men participating in the Normative Aging Study. Participants had all been health screened at the onset of the study in the 1960s to exclude individuals with asthma or other chronic respiratory diseases. Respiratory symptoms were grouped into three categories: asthma (adult onset) and other wheezing syndromes; cough and phlegm production; and hay fever. Multivariate logistic regression models were utilized to assess the independent relationship of each phenotypic marker to symptom prevalence adjusted for age, cigarette smoking, and the competing influence of the other markers. In this population, the prevalence of each symptom increased with serum total IgE concentration, this relationship being strongest for asthma. Skin test positivity (greater than or equal to 5 mm induration to one or more aeroallergens) was strongly associated with hay fever but was not significantly associated with symptoms of wheeze or cough and phlegm. Eosinophilia was associated with asthma and with phlegm production. The association of eosinophilia with phlegm production was present in skin test-negative as well as skin test-positive subjects and remained significant even after current smokers and individuals with asthma or hay fever were excluded. These data support the concept that asthma and hay fever are related to different immunologic host factors as reflected by expression of atopy phenotypes. Future investigations of immunologic factors in respiratory disease susceptibility should include, at a minimum, an assessment of all three phenotypic markers of atopy.

Adult

Latent deficiency of the hematopoietic microenvironment of aged mice as revealed in W/Wv mice given +/+ cells.

The macrocytic anemia of W/Wv mice can be cured by injection of +/+ bone marrow cells (BMC) from WBB6F1 mice. However, it has been observed that some W/Wv recipients appear to "lose" their cure with time, an effect that does not appear to be related to the age of the BMC donor. The present study was undertaken to determine the effect of recipient age on W/Wv responses to BMC injection. The effect of aging on erythroid parameters was similar in untreated W/Wv mice and +/+ controls. In both genotypes, hematocrit (HCT) and red blood cell count (RBC) decreased, and the modal red blood cell size (peak) increased between 13 and 150 weeks of age. As anticipated, mean HCT and RBC values were lower and peak values higher in W/Wv mice compared to +/+ controls at every age. However, the rate of decrease in HCT and RBC with age was the same for both genotypes, suggesting that the age effect and W gene effect were independent. Peak values increased slightly more with age for W/Wv than for +/+ controls. When female W/Wv mice in three age groups (23.5, 70, and 91.5 weeks old) were injected with 5 x 10(5) BMC from 20-week-old +/+ female donors and HCT, RBC, and peak were determined monthly, improvement was seen in most W/Wv recipients. However, in the older mice this improvement was slower and often was not sustained; 100% of the youngest recipients, 80% of the middle-aged, and only 30% of the older groups were cured after 3 months. Taken together, these data suggest a latent deficiency of the aging hematopoietic microenvironment that is revealed in W/Wv mice by the stress of continuing erythroid demand on the limited number of normal donor BMC.

Aging

Cardiac contusion in pediatric patients with blunt thoracic trauma.

To investigate the prevalence of myocardial contusion associated with blunt chest trauma in the pediatric age group, all patients admitted to our institution during a 6-month period with blunt thoracic trauma severe enough to produce a pulmonary contusion or rib fracture were prospectively evaluated. Cardiac evaluation was undertaken, including a multiple-gated acquisition (MUGA) cardiac scan, serial electrocardiograms (ECG), and serum creatine phosphokinase (CPK) and CPK isoenzymes. Seven patients, ranging in age from 2 1/2 to 18 years, with rib fractures or pulmonary contusion by chest roentgenograph were identified. One patient was injured as a passenger in a motor vehicle accident, five were struck by automobiles as pedestrians, and one sustained traumatic asphyxia when a car, supported by a jack, fell on his chest. All had at least one other major organ system injured. All patients had pulmonary contusions as determined by chest radiograph, and two had associated rib fractures. In 43% (three of seven) of patients, a significant cardiac contusion was identified, defined by abnormal right or left ventricular wall motion and a decreased ejection fraction on MUGA scan, and confirmed by an increase in cardiac enzymes and isoenzymes. However, in contrast with adults, no patients had ECG abnormalities. This limited series suggests that cardiac contusion may occur frequently in pediatric patients who have suffered from blunt thoracic trauma significant enough to result in pulmonary contusion. An MUGA scan provides a rapid, noninvasive assessment of cardiac damage in this setting. Further studies will be required to determine the clinical significance and long-term consequences of traumatic myocardial damage in the pediatric population.

Accidents, Traffic

High apical insertion of the right diaphragm in an infant with right-sided Bochdalek diaphragmatic hernia.

We report the case of a newborn full-term infant who presented to our service on the first day of life with a right-sided Bochdalek congenital diaphragmatic hernia associated with a high apical insertion of the right hemidiaphragm at the level of the second rib. This resulted in incarceration of the left lobe of the liver within the right hemithorax, but minimal pulmonary hypoplasia. A search of the literature failed to show a previous report of this variant of a duplication of the diaphragm in conjunction with a congenital diaphragmatic hernia. The approach taken for diaphragmatic reconstruction and closure of the defect is described.

Abnormalities, Multiple

T-cell subsets in healthy teenagers: transition to the adult phenotype.

Little is known about the normal range and variability of T-cell subsets in older children. We analyzed peripheral blood mononuclear cell subsets in 112 healthy children, ages 12-19 years (mean +/- SD: 15.4 +/- 1.9 years), using monoclonal antibodies and flow cytometry. The study population included 28 blacks and 84 whites, with 59 boys and 53 girls. The mean +/- SD cell subset values were: CD3+ T cells, 74.0 +/- 7.8%; CD4+ helper-inducer T cells, 46.8 +/- 6.9%; CD8+ suppressor-cytotoxic T cells, 27.3 +/- 5.7%; CD4:CD8 helper:suppressor ratio, 1.81 +/- 0.57; CD16+ natural killer cells, 4.4 +/- 3.1%; CD19+ B cells, 10.0 +/- 5.3%; CD14+ monocytes, 20.0 +/- 6.5%; and HLA-DR cells, 15.4 +/- 4.8%. Overall, boys had a higher proportion of HLA-DR+ cells than girls, attributable to an increase in CD19+ B cells. Blacks tended to have a higher proportion of HLA-DR+ cells than whites, apparently due to an increase in activated T cells. Detailed analysis by age group revealed a striking transition in the pattern of CD4+ and CD8+ cell populations. The CD4:CD8 ratio, higher in boys than girls for ages 12-16, was reversed to the "adult" pattern in 17-19 year olds, with a higher CD4:CD8 ratio in girls. These data provide important baseline values for healthy children and stress the importance of establishing normative ranges for pediatric subjects separately from adults.

Adolescent

The influence of donor age on graft survival in renal transplantation.

The current supply of kidneys from cadaver and living related donor sources is not sufficient to meet the demand. As a result, alternative sources of renal allografts are being explored, including very young donors and anencephalic newborns. However, data on the success of transplanting kidneys from very young donors are limited and conflicting. The purpose of this study was to determine whether the function and survival of renal grafts obtained from newborns and very young donors is different from that for grafts obtained from older donors. Thirty-six cadaveric donors under the age of 3 years, including seven anencephalic newborns, were evaluated. Allograft recipients ranged in age from 12 months to 57 years. The clinical outcome for these donor organs was compared with the graft survival for 136 kidneys transplanted from cadaver donors over age 3 years at our institution. There was a 65% 6-month and 64% 1-year graft survival in recipients of kidneys from donors greater than or equal to 3 years. Survival of grafts from donors under 12 months of age (n = 16) was significantly decreased compared with donors age 3 years and older, with a 31% 6-month (P less than .01) and 19% 12-month survival (P less than .001). Grafts obtained from anencephalic donors did not differ in survival or function from kidneys obtained from other donors less than 12 months of age. Survival for renal allografts from donors age 13 months to 3 years was also decreased relative to older donors: 55% at 6 months (P greater than .1) and 40% at 1 year (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The influence of age, race, and gender on peripheral blood mononuclear-cell subsets in healthy nonsmokers.

To investigate the influence of age, race, and gender on the cellular immune system, we determined T-cell, B-cell, monocyte, natural killer (NK)-cell, and HLA-DR+-cell subsets in 266 nonsmokers from a population-based random sample of healthy adults using monoclonal antibodies and flow cytometry. Blacks had a lower total white blood-cell count than whites (P less than or equal to 0.0001), due primarily to a decrease in granulocytes. There was no significant difference in absolute lymphocyte count between blacks and whites. Blacks had a higher proportion of CD19+ cells (Leu 12+ B cells) and a lower proportion of CD3+ cells (OKT3+ T cells) than whites (P less than or equal to 0.01). Female sex and increasing age were independently associated with an increased percentage of CD4+ cells (OKT4A+ helper-inducer T-cell subset), resulting in a higher helper/suppressor ratio among women and older individuals (P less than or equal to 0.05). Black race and increasing age were independently associated with an increased proportion of HLA-DR+ cells (P less than or equal to 0.0001) which was not attributable to B cells or monocytes. No significant age, race, or gender effects were observed for CD14+ cells (Leu M3+ monocytes) or CD16+ cells (Leu 11A+ natural killer cells). These data demonstrate that age, race, and gender are each associated with significant differences in peripheral blood mononuclear-cell subsets. Population-based data such as these provide an important foundation for future design and interpretation of human flow cytometry data.

Adult

Biochemical epidemiology in community-based studies: practical lessons from a study of T-cell subsets.

Elaborate laboratory tests are increasingly being incorporated into traditional epidemiologic research designs, a concept commonly termed biochemical epidemiology. Some of the issues encountered are illustrated by a recent population-based survey of healthy individuals in the Washington, D.C. area designed to examine the effects of demographic characteristics, lifestyle, and medical conditions on peripheral blood T-cell subsets. The study was conducted in three phases: selection of households by random digit dialing (Phase I); telephone interviews (Phase II), and self-administered questionnaires and phlebotomy (Phase III). Although this design facilitated the selection of the final study population, it influenced the participation rates by offering opportunities for nonresponse at each phase. Race was the strongest determinant of response rate despite the use of highly-trained, racially-matched telephone interviewers and repeated attempts at refusal conversion. Also discussed are issues of confidentiality, and logistics of biologic specimen collection and handling. The difficulties encountered in this survey are examined, with suggestions for future population-based investigations involving biochemical epidemiology.

Adult

A multivariate analysis of determinants of survival for patients with squamous cell carcinoma of the head and neck.

The prognosis for patients with squamous cell carcinoma of the head and neck remains poor, despite refinements in conventional therapy and experimental protocols using alternative treatment modalities. Clinical characteristics reported to influence survival have included age and sex of the patient, the therapy used, location of the primary tumor, and stage at initial presentation. However, such variables are highly correlated, and previous reports have lacked sufficient statistical analysis to assess the independent influence of these competing variables on survival. To better define the principal determinants of survival, we used a Cox multivariate regression analysis of 542 patients with invasive squamous cell carcinoma of the head and neck treated exclusively at our institution from 1962 to 1976. All patients were followed for a minimum of 5 years after diagnosis, with 98% complete follow-up achieved. Stage at initial presentation was the single-most important factor influencing survival for all tumor locations (p less than 0.0001). Advanced age (p = 0.001) and location of the primary tumor in the tonsillar area (p = 0.01) were also independently associated with an inferior survival. The type of therapy used and sex of the patient did not significantly influence survival after controlling for stage. These data emphasize the need for early diagnosis and treatment of squamous cell carcinoma of the head and neck and underscore the limitations of current therapeutic approaches. Future investigations should incorporate multivariate statistical techniques whenever possible, and additional efforts must be directed at basic research into the biology and immunologic characteristics of these tumors in an attempt to identify innovative therapeutic modalities.

Adult

Association of cigarette smoking with decreased numbers of circulating natural killer cells.

To investigate the relationship between cigarette smoking and the level of circulating natural killer (NK) cells, we studied 282 subjects from a population-based, stratified random sample of healthy persons. NK cells were enumerated by flow cytometry using the monoclonal antibody anti-Leu 11A. Cigarette smokers had a significantly lower proportion of NK cells than did subjects who had never smoked (5.5 +/- 0.3% versus 7.4 +/- 0.4% of lymphoid cells; p = 0.0002). NK cells were also decreased among ex-smokers (5.6 +/- 0.4%; p = 0.002), including subjects who had not smoked for more than 20 yr. The white blood cell and lymphocyte counts were increased in smokers compared with those in never smokers (p less than 0.0001). In contrast to NK cells, the smoking-related changes in leukocyte count were not present in ex-smokers, even those who had stopped smoking within the past year. Multivariate analysis confirmed that both current and past smokers had significant decreases in both the number and proportion of NK cells after controlling for age, sex, and lymphocyte count. These data indicate that cigarette smoking is associated with a decrease in the number and proportion of circulating NK cells, and that this effect is present many years after smoking cessation. This quantitative NK cell deficit may contribute to the elevated risk of malignancy in this population.

Adult

The effects of cigarette smoking on T cell subsets. A population-based survey of healthy caucasians.

To investigate the influence of cigarette smoking on mononuclear cell subsets, we determined T cell, B cell, monocyte, and HLA-DR+ subsets in a population-based, stratified, random sample of healthy Caucasians using monoclonal antibodies and flow cytometry. The study population consisted of 282 subjects 20 to 69 yr of age, including 108 smokers and 174 nonsmokers. Multivariate analysis techniques were used to assess the influence of cigarette smoking status after controlling for the effects of age and gender. Cigarette smoking was associated with a nonspecific increase in the leukocyte count involving all major cell types (smokers: 8.50 +/- 0.15 versus nonsmokers: 7.33 +/- 0.12 cells/mm3; p less than or equal to 0.0001). In addition, cigarette smokers had a selective increase in CD4+ cells (helper-inducer T cells) compared with nonsmokers (55.3 +/- 0.8 versus 52.2 +/- 0.6% of lymphoid cells; p = 0.002), resulting in a statistically significant increase in the CD4+/CD8+ (helper/suppressor) ratio (2.42 +/- 0.1 versus 2.13 +/- 0.16; p = 0.02). There was no significant difference between smokers and nonsmokers in the level of CD3+ cells (total T cells: 76.8 +/- 0.7 versus 76.1 +/- 0.5; p = 0.5), CD8+ cells (suppressor-cytotoxic T cells: 25.7 +/- 0.8 versus 27.0 +/- 0.5%; p = 0.1), CD19+ cells (B cells) (10.7 +/- 0.4 versus 10.0 +/- 0.3%; p = 0.2), CD14+ cells (monocytes) (18.0 +/- 0.6 versus 17.0 +/- 0.4%; p = 0.2), or HLA-DR+ cells (14.5 +/- 0.5 versus 14.0 +/- 0.4%; p = 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Use of a rapid differential stain for identifying Pneumocystis carinii in bronchoalveolar lavage fluid. Diagnostic efficacy in patients with AIDS.

Identification of Pneumocystis carinii involves silver stains which require several hours for processing. Diff Quik, a differential stain similar to Wright-Giemsa, requires less than 1 min and reproducibly stains trophozoites and intracystic bodies of P carinii. To determine the utility of DQ for rapid detection of P carinii in BAL fluid, we reviewed DQ-stained slides of 50 BAL samples from 36 patients seropositive for HIV+ who had undergone bronchoscopy with BAL for evaluation of interstitial pulmonary infiltrates. A comparison group of immunocompromised patients with P carinii pneumonia also were reviewed. For HIV+ samples, sensitivity of DQ was 93 and 100 percent for cytopathologists and 75 and 89 percent for pulmonologists. Specificity was 95 percent for each cytopathologist and 100 percent for pulmonologists. For non-HIV+ patients, sensitivity ranged from 22 to 55 percent. Thus, DQ may be useful as a rapid, reliable method to identify P carinii in BAL fluid from HIV+ patients.

Acquired Immunodeficiency Syndrome

Duplications of the alimentary tract. Clinical characteristics, preferred treatment, and associated malformations.

Duplications of the alimentary tract are unusual congenital anomalies that frequently present a diagnostic as well as therapeutic challenge to the surgeon. Because these lesions occur so infrequently, they are often not suspected until encountered intraoperatively. Due to the complicated anatomy and common blood supply shared between the duplication and associated native bowel, appropriate management requires a familiarity with the anatomy and clinical characteristics of this entity. To better define the range of patient characteristics, clinical presentation, and preferred therapy, 20 enteric duplications were reviewed in 17 patients treated at the Children's Hospital Medical Center from 1956 to 1986. Ages of patients ranged from 1 day to 11 years; 60% were less than 2 years of age at initial presentation. Seven duplications in six patients involved alimentary tract structures of foregut derivation (esophagus, stomach, and Parts I and II of duodenum), with a predominance of girls (4 of 6). Most of these patients (67%) presented with moderate to severe acute respiratory distress and a mass present on chest radiograph. In 67% of the patients, the correct diagnosis was established before operation. None required emergency operative intervention. By contrast, 13 duplications in 11 patients were of midgut or hindgut derivation (Parts III and IV of the duodenum, jejunum, ileum, and colon). In this group of patients, 62% of the duplications involved the cecum, 23% involved the ileum, and 16%, the jejunum. Seventy-eight per cent of the patients were boys. The most common symptoms were nausea and vomiting, and the most common sign was a palpable abdominal mass. Emergency operative intervention was required of eight of 11 patients with duplications involving the small bowel and colon. Three patients presented with an intussusception, four with signs and symptoms consistent with acute appendicitis, one with a small bowel obstruction, and two with gastrointestinal hemorrhage due to the presence of ectopic gastric mucosa within the duplication. It was found that two important points must be considered in regard to the management of enteric duplications: (1) the common blood supply shared between the duplication and native bowel must be carefully protected to avoid undue sacrifice of normal bowel, and (2) the presence of heterotopic gastric mucosa in 35% of patients negates internal drainage.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Multiple

Squamous cell carcinoma of the head and neck at the Massachusetts General Hospital: a comparison of biologic characteristics in men and women.

Little is known about the biologic behavior of squamous cell carcinoma of the head and neck in women. A few recent reports for selected sites have suggested that these tumors may be becoming more common in women. To evaluate potential differences between males and females with squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx and to assess whether the proportion of females with this disease is increasing, the authors have undertaken a retrospective review of 542 consecutive patients treated at our institution from 1962 through 1976. We report here the first detailed comparison of males and females with squamous cell carcinoma of the head and neck, with attention directed to stage at initial presentation, choice of therapy, response to therapy, age distribution, survival, and prevalence of second primary malignancies. It has been widely published that survival for women with squamous cell carcinoma of the head and neck is superior to that for men, and this has been attributed to a difference in the biologic characteristics of the disease between the two sexes. Although overall survival calculations in our series suggested a significantly better survival rate for women than for men, these rates were strongly influenced by the larger proportion of women (64%) who had stage I or II disease, compared with only 50% of men. When survival was compared stage by stage, there was no significant difference in survival between the two sexes. The proportion of females in the combined study population was 35%, increasing from 33% in the first 5 years of the study period to 40% in the last 5 years. Among patients born before 1920, 34% were female compared with 43% of patients born after 1920. Of the 13 patients less than 40 years of age at diagnosis, 62% were female. The rising proportion of women during the 15-year study period, particularly among young patients and those in more recent birth cohorts, strongly suggests that squamous cell carcinoma of the head and neck is increasing among women in this referral population. A review of the literature indicates that this trend began more than 40 years ago.

Adult