Mortality from multiple myeloma among North Carolina furniture workers.

The risk of multiple myeloma among furniture workers was investigated in a case-control study with the use of death certificate statements on occupation in North Carolina counties with heavy employment in furniture-manufacturing industries. From computerized mortality listings, 301 male deaths from multiple myeloma were identified, and 858 controls were selected from deaths due to other causes; controls were matched by sex, race, county of usual residence, age at death, and year of death. Employment in the furniture industry was associated with a nonsignificant excess risk of multiple myeloma [relative risk (RR) = 1.3], particularly among subjects who died before age 65 (RR = 1.7) and among those born before 1905 (RR = 1.5). A significantly elevated risk (RR = 5.4) was seen for furniture workers who were born before 1905 and died prior to age 65. Unexpectedly, farmers were found to have a significantly decreased risk of multiple myeloma (RR = 0.6). The finding of an elevated risk of myeloma in earlier cohorts of furniture workers may be a clue to the nature of the environmental exposure.

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.

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.

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.

Thrombocytopenia in the intensive care unit.

STUDY OBJECTIVE: To determine the prevalence of thrombocytopenia in an ICU and assess which factors were associated with thrombocytopenia. DESIGN: A review of the medical records of patients admitted during 3 separate months during 1 academic year. Patients must have survived at least 12 h in the ICU. SETTING: A medical ICU at a university hospital. PATIENTS: General medicine patients admitted to the ICU. INTERVENTIONS: All medical records were reviewed. During the ICU stay, daily medications, events, and platelet count were noted. All patients were followed up until death or hospital discharge. In 22 patients, including 18 who had thrombocytopenia, bone marrow aspirates were performed. MEASUREMENTS AND RESULTS: One hundred sixty-two admissions were evaluated. Thirty-eight (23 percent) had platelet counts less than 100,000/mm3 at least once, and 17 (10 percent) patients had platelet counts less than 50,000/mm3. Several factors were associated with thrombocytopenia; however, only sepsis, use of antineoplastic chemotherapy, elevated creatinine level, or elevated bilirubin value were independent risk factors for severe thrombocytopenia. In only one patient were the bone marrow findings different from those expected by the clinical presentation. Thrombocytopenia was associated with longer hospital stay (p < 0.001) and higher mortality (p < 0.001). CONCLUSION: Thrombocytopenia is a common occurrence in the ICU, usually due to the underlying disease, and is associated with an increased mortality.

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.

A murine model for assessing the respiratory hypersensitivity potential of chemical allergens.

Using equimolar quantities of 2 chemical allergens, toluene diisocyanate (TDI), noted for its ability to cause respiratory hypersensitivity, and dinitrochlorobenzene (DNCB), noted for its dermal sensitizing activity, the mouse was evaluated as a possible model to indicate respiratory hypersensitivity. A previously published procedure (Garssen et al. (1989) Immunology 68, 51-58) was followed whereby chemicals were applied epicutaneously to the shaved flank of BALB/c mice. Eight days later, animals were challenged by intranasal application of the chemical. The lungs were evaluated at 48 h. Both TDI and DNCB elicited mild mononuclear inflammatory cuffing around pulmonary vasculature. No reaction was noted around pulmonary airways. Sera, drawn 48 h following the intranasal challenge with chemical allergen, were evaluated for total IgE, hapten-specific IgE and IgG, and for IL-2, IL-4, IL-5, IL-6, and interferon gamma. Animals exposed to TDI demonstrated decreased total IgE and the presence of TDI-specific IgG. Cytokine levels were unchanged in both groups. These results indicate that in this mouse model, total serum IgE and the production of hapten-specific IgG antibodies distinguished a respiratory from a contact sensitizing chemical. Further comparison of the serologic response of mice to these two classes of chemicals is required to determine if the murine model can be used to predict dermal versus respiratory sensitizing activity of chemical allergens.

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.

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)

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.

The health effects of automobile exhaust. VI. Relationship of respiratory symptoms and pulmonary function in tunnel and turnpike workers.

To examine the effect of automobile exhaust on respiratory symptoms and pulmonary function, the authors studied 175 tunnel and turnpike workers employed by the Massachusetts Turnpike Authority on two occasions 3 yr apart beginning in 1972. A standard respiratory symptom and illness questionnaire was administered, spirometry was performed, and proximal hair lead and blood lead content were measured as biologic indices of automobile exhaust exposure. One hundred nine (63%) workers were current cigarette smokers, 41 (23%) were exsmokers, and 24 (14%) had never smoked. Smoking was strongly related to respiratory symptoms of cough (P less than .001) and phlegm production (P less than .001), but not to wheezing (P = .41), breathlessness (P = .14), bronchial asthma (P = .13), or frequent chest colds (P = .14). When workers were stratified by smoking status, no effect could be seen between high automobile exhaust exposure as measured by a variety of parameters and all of the above respiratory symptoms and illnesses. The level of pulmonary function [forced expiratory volume in 1 sec (FEV1.0) and forced vital capacity (FVC)] was not related to past or current exhaust exposure in a cross-sectional analysis when we controlled for age, height, and cigarette consumption. In a prospective analysis of 84 of these workers, the observed changes in FEV1.0 and FVC over 3 yr were unrelated to exhaust exposure after controlling for age, height, cigarette consumption, and initial level of pulmonary function.

[Chemiluminescence assays for cytokines in serum: influence of age, smoking, and race in healthy subjects].

Evidence is accumulating that cytokines are important intermediates in the pathogenesis of many diseases such as asthma and pulmonary fibrosis. However, a major limitation to clinical studies of cytokines has been the inability to measure these important biomarkers in serum from normal, healthy controls. Without this capability, interpretation of apparently elevated levels in problematic, and evaluation of diseased level is impossible. We have recently developed chemiluminescence ELISA (CL-ELISA), resulting in a 100-fold increase in sensitivity. To assess the influence of age, smoking, and race on serum cytokine levels in healthy population, we measured IL-4, 5, 6, 10, IFN-gamma, and GM-CSF in serum of healthy Japanese (n = 38), and Americans (n = 10) using CL-ELISA. In this small population with narrow age range, no difference between smokers and nonsmokers was found for any cytokine. No correlations between age and cytokines was demonstrated. However, Japanese samples had lower levels of IL-4, 5, and 10 than American samples. Further evaluation using more controlled study design and larger populations will be necessary to determine whether this difference is due to inherent racial differences in Th2 cell function.

Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance.

The immunoregulatory properties of hematopoietic stem cells (HSCs) have been recognized for more than 60 years, beginning in 1945, when Owen reported that genetically disparate freemartin cattle sharing a common placenta were red blood cell chimeras. In 1953, Billingham, Brent, and Medawar demonstrated that murine neonatal chimeras prepared by infusion of donor-derived hematopoietic cells exhibited donor-specific tolerance to skin allografts. Various approaches using HSCs in organ transplantation have gradually brought closer to reality the dream of inducing donor-specific tolerance in organ transplant recipients. Several hurdles needed to be overcome, especially the risk of graft-versus-host disease (GVHD), the toxicity of ablative conditioning, and the need for close donor-recipient matching. For wide acceptance, HSC therapy must be safe and reproducible in mismatched donor-recipient combinations. Discoveries in other disciplines have often unexpectedly and synergistically contributed to progress in this area. This review presents a historic perspective of the quest for tolerance in organ transplantation, highlighting current clinical approaches.

Managed care in workers' compensation plans.

Workers' compensation plans have lagged behind most public and private health care plans in the adoption of managed care techniques. This is largely attributable to the underlying differences between workers' compensation and group health plans. Managed care techniques were developed within group health plans with the objective of health at the lowest cost. In workers' compensation, managed care must address a different objective-restoring a worker to health and productivity at the lowest cost. It is this fundamental difference that makes the application of managed care techniques to workers' compensation plans contentious and at times inappropriate. Research on the impact of managed care on the health and welfare of injured workers is sparse, and important questions remain about the appropriateness of care delivered under workers' compensation managed care plans. In this paper, we discuss the application of managed care to workers' compensation, and highlight the barriers to effective implementation.

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.

Endometrial Th2 cytokine expression throughout the menstrual cycle and early pregnancy.

Embryonic implantation and maintenance of pregnancy is influenced by the maternal immunological response. Type 2 T-helper (Th2) cells secrete interleukins 4, 5, 6 and 10 and are associated with suppression of cell-mediated immunity. Temporal changes in the expression of these cytokines were detectable by immunohistochemistry throughout the menstrual cycle. In pregnancy, 10-fold or greater increases in interleukin 6 and 10 secretion were detectable by enzyme-linked immunoassay compared with the non-pregnant state. The pattern of expression of Th2 cytokines suggests that progesterone may influence endometrial cytokine secretion. During pregnancy, Th2 expression paralleled that of vimentin, a stromal cell marker, suggesting that these cells may be a principal source of Th2 cytokines may be a mechanism of suppressing cell-mediated immunity in the endometrium, which may in turn enhance embryonic implantation and maintenance of pregnancy.

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.

The association of ambient air pollution with twice daily peak expiratory flow rate measurements in children.

A stratified sample of 83 children living in Uniontown, Pennsylvania, reported twice daily peak expiratory flow rate (PEFR) measurements on 3,582 child-days during the summer of 1990. Upon arising and before retiring, each child recorded the time, three PEFR measurements, and the presence of cold, cough, or wheeze symptoms. Ambient air pollution, including particle-strong acidity, was measured separately during the day (8 a.m. to 8 p.m.) and at night. Each child's maximum PEFR for each session was expressed as the deviation from his or her mean PEFR over the study and adjusted to a standard of 300 liters/minute. The session-specific average deviation was then calculated across all of the children. A second-order autoregressive model for PEFR was developed, which included a separate intercept for evening measurements, trend, temperature, and 12-hour average air pollutant concentration weighted by the number of hours each child spent outdoors during the previous 12-hour period. The results are expressed in terms of the interquartile range for each pollutant. A 12-hour exposure to a 125-nmol/m3 increment in particle-strong acidity was associated with a -2.5 liters/minute deviation in the group mean PEFR (95% confidence interval (CI) -4.2 to -0.8) and with increased cough incidence (odds ratio (OR) = 1.6, 95% CI 1.1 to 2.4). A 30-ppb increment in ozone for 12 hours was associated with a similar deviation in PEFR levels (-2.8, 95% CI -67 to 1.1). The association between PEFR and particle-strong acidity was observed among the 60 children who were reported as symptomatic on the prior symptom questionnaire (-2.5, 95% CI -4.5 to -0.5). The authors conclude that summer occurrences of excessive acid aerosol and particulate pollution are associated with declines in peak expiratory flow rates in children.

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.