Usefulness of omalizumab in ten patients with severe occupational asthma.

BACKGROUND: The management of severe occupational asthma (OA) remains problematic and new alternative treatments providing better disease control are required, ideally enabling affected individuals to remain in their job. METHODS: Ten patients with severe uncontrolled OA were treated with the monoclonal anti-IgE antibody omalizumab. In six cases the causative agent was a high molecular weight (HMW) compound and in four cases it was a low molecular weight (LMW) chemical. All of the patients had well documented OA despite workplace adjustments. RESULTS: During treatment, nine patients exhibited a lower rate of asthma exacerbations and used less oral or inhaled corticosteroids. Seven patients were able to continue working at the same workplace as before treatment. CONCLUSION: We have demonstrated that omalizumab is a potential treatment for severe uncontrolled OA and enabled seven of the ten patients in the study to remain in their job.

Low calcium and vitamin D intake in healthy children and adolescents and their correlates.

BACKGROUND: Optimal dietary calcium and possibly vitamin D intake throughout childhood and adolescence may enhance bone mineral accrual. Little data on the intake of these nutrients in Mediterranean countries exist, and predictors of their suboptimal intake are not well defined. OBJECTIVE: To evaluate systematically the effect of gender, lifestyle factors, and socioeconomic status on mean calcium and vitamin D intake in healthy school children and adolescents from Lebanon. DESIGN: A total of 385 students aged 10-16 y were selected from four public and four private schools between Fall 1999 and Spring 2000. Information on calcium and vitamin D intake, through a semiquantitative food frequency questionnaire that was validated against a 7-day daily record, and on socioeconomic and lifestyle factors were obtained. RESULTS: Only 12% of the students met the adequate intake (AI) recommendation of 1300 mg of calcium/day, and only 16% met the AI recommendation of 200 IU of vitamin D/day. Boys had a significantly higher mean daily calcium intake than girls. Socioeconomic status as assessed by children's pocket money was a predictor of higher calcium and vitamin D intake. Eating breakfast and physical activity were other correlates of daily calcium and vitamin D intake. CONCLUSIONS: Only a minority of students in our study met the AI for calcium and vitamin D. Gender, lifestyle factors, and socioeconomic status were significant predictors of calcium and vitamin D intake. Our findings have important implications regarding the institution of dietary public health strategies to promote skeletal health in Mediterranean countries during a critical time for bone mass accrual.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Quantitation of chemotactic factor generation in human sera.

Increased sensitivity of chemotaxin titration in the 'migration under agarose' method was achieved by reduction in agarose concentration of the medium from the conventional 1.0% to 0.5%. Satisfactory technical properties of the gel were achieved by inclusion of 2.0% bovine serum albumin. The modificatin resulted in increased migration rates and greater reproducibility than those achieved with other media. The range of normal values was established by study of sera of 20 normal adults with use of a single batch of target cells. It is concluded that under the conditions described, a difference in chemotactic differential of 10% or more between a serum sample submitted for assay and that of pooled serum from normal subjects is statistically significant.

Late effects in children treated with radiation therapy for Wilms' tumor.

PURPOSE: To determine the frequency and types of late effects in children receiving radiation therapy (RT) for Wilms' tumor. MATERIALS AND METHODS: From 1968 to 1994, 55 children received megavoltage RT at our institution as part of treatment for Wilms' tumor. A total of 42 (76.4%) have survived and have a minimum follow-up of 5 years. There were 25 female and 17 male patients with a median age at diagnosis of 48 months (range, 7-126 months). There were 12 Stage I, eight Stage II, 15 Stage III, six Stage IV, and one Stage V patient. RT was delivered to the hemiabdomen in 36 and whole abdomen in six patients. RT dose was 1000-1200 cGy (Group A) in 12, 1201-2399 cGy (Group B) in 11, and 2400-4000 cGy (Group C) in 19. Whole-lung RT was delivered to 13 patients either at diagnosis or pulmonary relapse. All patients received chemotherapy; the most common agents were actinomycin-D/vincristine/adriamycin in 13 and actinomycin-D/vincristine in 18. Median follow-up was 181 months (range, 60-306 months). RESULTS: Of 42 patients, 13 (31.0%) did not have late effects of treatment. The number of patients who developed muscular hypoplasia, limb length inequality, kyphosis, and iliac wing hypoplasia were seven (16.7%), five (11.9%), three (7.1%), and three (7.1%), respectively. Scoliosis was seen in 18 (42.9%) with only one patient requiring orthopedic intervention. Median time to development of scoliosis was 102 months, with a range of 16-146 months. The actuarial incidence of scoliosis at 5, 10, and 15 years after RT was 4.8 +/- 3.3%, 51.8 +/- 9.0%, and 56.7 +/- 9.3%, respectively. Only one of 12 Group A patients developed scoliosis. The 10- and 15-year actuarial incidences of scoliosis for Group A and B patients were 37.7 +/- 12.4% and 37.7 +/- 12.4%, whereas for Group C patients the incidences were 65.8 +/- 12.0% and 74.4 +/- 11. 7% (p = 0.03, log rank test). The actuarial incidence of bowel obstruction at 5, 10, and 15 years was 9.5 +/- 4.5%, 13.0 +/- 5.6%, and 17.0 +/- 6.5%. Of 23 patients, five irradiated within 10 days of surgery and one of 19 irradiated after 10 days developed bowel obstruction (p = 0.09, log rank test). Three patients developed hypertension with normal blood urea nitrogen (BUN) and creatinine levels; another patient had chronic renal insufficiency in a nonirradiated kidney. One patient developed diffuse interstitial pneumonitis. Of the 19 female patients who have reached puberty, three have given birth, and 15 have regular and one has irregular menstrual periods. Four patients developed benign neoplasms; three were in the RT field (two osteochondroma, one lipoma) and one outside (cervical intraepithelial neoplasia II). There were three second malignancies (chronic myelogenous leukemia at 9 years, osteosarcoma at 11 years, and breast cancer at 25 years after initial diagnosis of nephroblastoma); both solid malignancies occurred in the RT field. CONCLUSIONS: Late effects of therapy were seen in more than two thirds of children treated for Wilms' tumor. Children treated with lower doses (<2400 cGy) had a lower incidence of scoliosis compared with those who received more than 2400 cGy. There is also a suggestion that the incidence is lower in patients who received 1000-1200 cGy. Severe physical and functional deformity from RT was uncommon.

Health outcomes of a community-based therapy program for children with cancer--a shared-management approach.

Critical to providing cancer therapy to children in rural areas is finding dependable sources of therapy near the patients' homes. In this study, comparison was made of 668 visits by 24 patients to nearby private practitioners, who carried out 70% of the therapy, with 712 visits by 22 other patients for whom all care was managed by pediatric hematologist-oncologists. There was no significant difference by Wilcoxon rank sum test between the two groups in the accuracy with which protocol rules were followed, in the incidence of neutropenia, infection, fever, thrombocytopenia, drug toxicity, or the proportion of days hospitalized. The findings indicate that the private practitioners participating in a shared-management system were a dependable resource for providing 70% of the total cancer therapy to these patients.

Sex-specific criteria for interpretation of thallium-201 myocardial uptake and washout studies.

A study was undertaken to determine the effect of gender on criteria for the quantitative analysis of exercise-redistribution 201Tl myocardial scintigraphy. The studies of 26 normal females and 23 normal males were subjected to bilinear interpolative background subtraction and horizontal profile analysis. Significant sexual differences were found in both regional uptake ratios and washout rates. These differences primarily reflected a proportionately decreased anterior and upper septal uptake in females, and faster washout in females. Faster myocardial 201Tl washout rates in females could not be clearly ascribed to either a physiological or artifactual explanation. It is concluded that since important differences exist between males and females in the detected pattern of 201Tl myocardial uptake and washout, sex-specific criteria may enhance the predictive accuracy of exercise-redistribution 201Tl myocardial scintigraphy.

Acute monoblastic leukemia: a unique subtype--a review from the Childrens Cancer Study Group.

The acute non-lymphocytic leukemias (ANLL) are generally treated as a homogeneous group. However, the literature is replete with articles alluding to distinctive features of acute monoblastic leukemia (AMoL). This review addresses the unique clinical, laboratory, epidemiological, and therapeutic features of AMoL. Leukemic monoblasts are distinguished from other cells in the myelocytic series by physical properties such as greater adhesiveness, deformability, and motility. Patients with AMoL often exhibit hyperleukocytosis, disseminated intravascular coagulation, and extramedullary involvement, particularly in the skin, gingiva, and central nervous system (CNS). AMoL occurs predominantly in adults over 40 and children under 10, fifty percent of whom are under 2 years of age at diagnosis. Its relatively common occurrence in infants parallels the high rate of proliferation of monocytes in that age group. Additionally, its occurrence in young children appears to be associated with in utero exposure to marijuana and parental exposure to pesticides and solvents. Therapeutic results are generally poor due to high rates of fatal complications during induction, induction failures, and frequent extramedullary and medullary relapses. This poor outcome is particularly noted in infants. Higher remission induction rates attained with epipodophyllotoxins and incorporation of bone marrow transplantation have not yet resulted in substantial improvement of long-term outcome. Recurrence of disease in the CNS is minimized by the use of intensive CNS presymptomatic treatment, usually incorporating irradiation. Our review suggests that unique and innovative treatment strategies are needed to improve outcome for patients with AMoL.

Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder characterized by pancreatic insufficiency, short stature, skeletal abnormalities and bone marrow dysfunction. Patients with SDS have varying degrees of marrow aplasia, which can be severe or progress to leukemic transformation. While allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for the hematologic disturbances of SDS, a recent review of the literature reveals few survivors. Poor outcome with HSCT is often related to excessive cardiac and other organ toxicity from transplant preparative therapy. We describe two young children with SDS who developed aplastic anemia and subsequently underwent successful allografting using a non-cardiotoxic conditioning regimen. Case 1 received marrow from an HLA-identical sibling while case 2 received partially matched umbilical cord blood from an unrelated donor. Both patients are presently alive and well with sustained donor engraftment and excellent hematopoietic function at 36 and 22 months post-HSCT.

Nonendemic adult T-cell leukemia/lymphoma in the United States: report of two cases and review of the literature.

Adult T-cell leukemia/lymphoma (ATLL) is a recently described distinct clinicopathologic entity characterized by a leukemic or lymphomatous proliferation of hyperlobulated peripheral T-cells, which is usually widespread at presentation and is associated with infection by a type C retrovirus. ATLL rarely is described outside of endemic regions, which include southwestern Japan, the Caribbean region, and the southeastern United States. The authors report the clinical, pathologic, and immunologic features of two cases of nonendemic ATLL that occurred in patients from the midwest United States. One patient was a 16-year-old white girl from rural Iowa, and the other was a 46-year-old white man from rural Minnesota. The features of 13 other probable nonendemic ATLL cases from the United States were compiled and reviewed. In the United States, nonendemic ATLL occurred in widespread geographic locations, affected mostly white people, and was characterized by an aggressive course with generalized adenopathy, blood and bone marrow involvement, and hepatosplenomegaly at presentation. Skin involvement was present in one-fourth of the patients. Hypercalcemia was rare. Although antibodies to type C retrovirus were detected in three of the five patients tested, the available data is not sufficient to establish a conclusive association between nonendemic ATLL and type C retrovirus infection.

Shared management of children with cancer.

OBJECTIVE: To determine the risks and benefits of university-based pediatric oncologists and community-based primary care physicians sharing the management of children with cancer. DESIGN: Physicians participating in shared management of children with cancer were surveyed, and the outcomes of the children were measured. SETTING AND PARTICIPANTS: One hundred thirty-seven community-based primary care physicians participated in the management of the 226 children with cancer in Iowa and western Illinois during the past 15 years. The survival of the 226 children was compared with that of 240 randomly selected children treated using the identical treatment protocols but treated only by pediatric oncologists. INTERVENTION: A 7-point Likert scale questionnaire was completed by 97 (71%) of the participating primary care physicians. RESULTS AND OUTCOME MEASURES: There were no differences in the survival of children using shared management compared with those treated only by pediatric oncologists. Primary care physicians believed that shared management is of economic and psychosocial benefit to patients, improves the treatment choices available to patients, does not require excessive time, and does not result in loss of practice income. The system strengthens the primary care physicians' relationships with oncologists and results in additional referrals to the university-based pediatric oncologists. It is of educational value, is personally satisfying, and provides relief from the stress associated with caring for these families. Primary care physicians would like to see this system expanded to include other children with special health care needs. CONCLUSION: The shared-management approach to care is a viable attractive option of health care provision for children.

Hospital dietetics and food service in developing countries: I. The Middle East.

A survey of hospital food service and dietetics was conducted in the largest hospitals of six Middle Eastern countries: Bahrain, Jordan, Kuwait, Lebanon, Saudi Arabia, and Syria. There were very few individuals with training in food service and dietetics in any of the countries. The effect of this lack of training on hospital food service and dietetics is discussed. Recommendations are made that would result in improvements in hospital food service and dietetics in the Middle East.

Hospital dietetics and food service in developing countries: III. Bangladesh.

A survey of 11 hospitals in Bangladesh revealed that most heads of hospital food service had little or no training in nutrition and dietetics, hospital diets were usually inadequate, therapeutic diets were seldom used, and kitchen sanitation was poor. However, in three hospitals in which the heads of food service had some education in nutrition, conditions were markedly better. Even though the results of this survey suggest that major improvements are needed in hospital food service and dietetics in Bangladesh, extensive training programs are probably unrealistic because of the limited economic base of the country. Short-term inservice training programs could result in marked improvement in the quality of food service, sanitation, and the use of therapeutic diets.

Hospital dietetics and food service in developing countries: II. Lebanon.

A survey of 15 hospitals in Lebanon revealed that food service personnel in most hospitals had no training in nutrition, dietetics, or food service management. Kitchen sanitation was inadequate. Therapeutic diets were usually incorrectly planned and seldom used. The need for training food service personnel was recognized only in hospitals with some trained persons on the staff.

[The cancer registry at the Hôtel Dieu de France Hospital]. / Registre du cancer à l'Hôtel Dieu de France.

Between January and December 1989, 541 new cases of cancer have been diagnosed at Hôtel-Dieu de France Hospital at Beirut. These cases were among 5400 histopathologic or hemato-cytologic examinations performed during the same period. There were 311 men (57.5%) and 230 women (42.5%). In men lung cancer was the most common site (19%) followed by bladder cancer (16.7%) and prostate cancer (11.6%). In women the most frequent cancer reported was breast cancer (36.1%) followed by uterine (body and cervix) cancer (15.2%) and digestive tract tumors (12.3%). Hematologic malignancies were more frequent between children and young patients. We have noted a progressive frequency of breast, lung, digestive tract, bladder and genito-urinary cancers with age. The establishment of a national tumor registry covering all diagnosed patients in different Lebanese Institutions is warranted.

Acquired chemotactic inhibitors during infection with guinea pig cytomegalovirus.

Factors involved in neutrophil and monocyte migrations were serially studied in strain 2 guinea pigs undergoing initial cytomegalovirus infection and sham-inoculated controls. All studies remained unchanged in uninfected animals. Monocyte migrations and neutrophil spontaneous migration remained unchanged in infected animals. However, transient abnormalities occurred early in infection, comprising a decrease in neutrophil-directed migration towards C5-derived chemotactic fractions (C5-fr) and a decrease in the chemotactic activity of zymosan-activated plasma. Consequently, the presence of neutrophil- and chemotaxin-directed inhibitors in plasma was investigated. Normal neutrophils, C5-fr, Escherichia coli-derived bacterial factor, and the synthetic peptide F-met-leu-phe were first incubated with control or infected plasmas and then assayed for directed migration and lysosomal enzyme release. Results indicated the de novo appearance of both neutrophil- and chemotaxin-directed inhibitory activities in plasma during early infection. The neutrophil-directed inhibition was heat stable (56 degrees C for 120 min) and nonspecific (responses to all chemotaxins were inhibited). The chemotaxin-directed inhibition was heat stable and C5-fr specific. The cytomegalovirus-induced inhibitors may be important in the enhanced susceptibility to concurrent opportunistic infections.

Role of chemotactic factor inactivation in neutrophil chemotaxis.

CFIs have been implicated in the regulation of several inflammatory mediators; consequently, we have evaluated the effects of CFI on neutrophil chemotactic and lysosomal enzyme release response to C5-derived chemotaxins. Chemotaxis was measured by direct migration under agarose, LER by glucosaminidase release from cytochalasin B-treated neutrophils, and CFI activity by its inhibition of LER. After inactivation by CFI, C5-fr lost their ability to stimulate neutrophils, and acquired a new chemotactic inhibitory activity. On gel chromatography, the stimulatory activity of C5-fr and the inhibitory activity of inactivated C5-fr eluted as separate peaks with different molecular weights. Effects of CFI on neutrophil responses to C5-fr, ZAS, and ZAP were adverse and dose-dependent: maximal neutrophil response to C5-ft decreased in amplitude as CFI levels increased, and a close reciprocal relationship was demonstrated between the endogenous CFI and the chemotaxis activities of ZAS (r = -0.833) and ZAP (r = -0.932) in 10 healthy adults. The data suggest that CFI is a potent regulator of neutrophil response to C5-derived inflammatory mediators.

Decreased chemotactic activity in activated newborn plasma.

The roles of complement levels and CFI activity in the regulation of chemotactic factor generation were evaluated in newborn and adult plasmas. Plasma samples were obtained from 19 healthy adults, 19 neonates, and 12 3-day-old infants. CFI levels were determined in all samples, chemotactic activity in 15 of the 19 adult and newborn samples, and complement levels in 10 of these 15. Compared to adult plasmas, CFI activity was higher in newborn and infant plasmas and chemotactic activity was lower. A close reciprocal relationship was shown between these two activities (r=-0.958). When corrected for the effects of CFI, the difference in chemotactic activity between newborns and adults disappeared. Mean levels of C1, C3, C4, C5, C3 to C9, CH50, factor B, and properdin were lower in newborn plasmas; however, C2 levels were higher. Partial correlations between these complement components and the chemotactic activity were of small magnitude and statistically not significant. These data suggest that higher CFI activity, rather than lower complement levels, accounts for most of the differences in chemotactic activity between newborn and adult plasma. (J Lab Clin Med 99:331, 1982.)