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.

Evaluating the effectiveness of epoetin alfa in community oncology practices.

PURPOSE: This retrospective case-series review studied the effectiveness of epoetin alfa in community oncology practices, which until now has not been well documented. METHODS: We reviewed the medical records of 118 cancer patients treated between 1999 and 2001 with cyclic chemotherapy plus epoetin alfa in 27 US community-based oncology practices. Two analysis sets were examined: one including all patients (n=118) and one including only those patients with no concurrent events impacting hemoglobin data interpretation (n=73). Efficacy of epoetin alfa was evaluated by hemoglobin response (aS2 g/dl increase in hemoglobin from baseline) at weeks 12 and 16, the time to hemoglobin response, and change in hemoglobin concentrations from baseline at specific time points. RESULTS: After 12 weeks of treatment, 43% (95% confidence interval [CI], 33-54%) of patients had a hemoglobin response, and the proportion of responders further rose to 61% (95% CI, 49-72%) after 16 weeks. The median time to response was 92 days (lower 95% confidence limit, 74 days; upper bound not estimable). Hemoglobin increased from baseline at all time points evaluated during epoetin alfa treatment, with a mean increase of 1.1 g/dl (95% CI, 0.77-1.4 g/dl) by the last observation. CONCLUSION: These results indicate that epoetin alfa is effective in community practice, but most patients take longer than 3 months to respond. Because slow responses may negatively impact on the quality of life in these patients, alternative treatment approaches providing faster and perhaps better responses may provide greater clinical benefit.

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.

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.

Hypovitaminosis D in healthy schoolchildren.

BACKGROUND: Vitamin D is essential for skeletal growth, but there are currently no guidelines for vitamin D supplementation after infancy. This study investigates vitamin D insufficiency in healthy children. METHODS: Children ages 10 to 16 years from 3 private schools in Beirut, Lebanon, with differing socioeconomic status (SES) were studied: 169 in the spring of 1999 and 177 in the following fall; 83 students participated in both study phases. They had a physical examination, answered a dietary questionnaire, and blood was drawn for calciotropic hormones and indices of bone turnover. RESULTS: Overall, 52% of the students were vitamin D-insufficient; the proportion of insufficiency was 65% in the winter and 40% at the end of the summer. During both seasons, girls had lower vitamin D levels than did boys; those who followed the dress code of covered head, arms, and legs had the lowest levels. Students in the mid-SES school had lower 25-hydroxyvitamin D (25-OHD) levels than did the ones from the high-SES school. After adjusting for confounders, gender, SES, and body mass index remained the significant predictors of vitamin D levels in both seasons (R(2) = 0.53, for spring and 0.28 for fall). There was a significant inverse correlation between 25-OHD levels and parathyroid hormone levels that was best fitted by a curvilinear model (R(2) = 0.19). CONCLUSION: Even in a sunny country, hypovitaminosis D is common in schoolchildren, more so in the winter. Girls, especially those with a lower SES, are at particular risk. The inverse changes in parathyroid hormone suggest that insufficient vitamin D levels may deleteriously affect skeletal metabolism in healthy adolescents. Vitamin D insufficiency may be prevalent in many other countries where supplementation of milk with vitamin D is not mandatory. Our results call to a reconsideration of vitamin D supplementation in high-risk adolescents to further optimize skeletal health. vitamin D insufficiency, bone metabolism, nutrition, gender, socioeconomic status.

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.

Relationship of dietary intake to DDE residues in breast milk of nursing mothers in Beirut.

Milk samples were collected from 32 nursing mothers living in the Beirut area, Lebanon. Dietary intakes of participating mothers were obtained from data of their diet histories, 24 h dietary recalls and food frequency questionnaires. Milk samples were screened for the presence of organochlorine pesticide residues and DDE levels were estimated using gas chromatographic techniques. The relationship between consumption of various food groups and DDE content of milk was investigated. A positive correlation was found between the consumption of either/or high fat meat, tuna fish and DDE levels in milk. Consumption of poultry products showed a weak correlation with DDE content of milk, whereas consumption of vegetable oils showed a negative correlation.

Color Doppler of the splenic artery in the prenatal diagnosis of heterotaxic syndromes.

The objective of this paper is to determine whether color and pulsed Doppler of the splenic artery is helpful in the prenatal diagnosis of polysplenia or asplenia in heterotaxic syndromes. Over a 3-year period, localization of the splenic artery by color and pulsed Doppler was attempted on all fetuses with the diagnosis of heterotaxic syndromes. Postnatal follow-up was obtained on all neonates. The diagnosis of heterotaxic syndromes was performed on eight fetuses during the study period. Mean gestational age at diagnosis was 20.1 weeks. All fetuses had situs ambiguous and complex cardiac abnormalities. All pregnancies were managed expectantly and none were terminated. The splenic artery was imaged by color and pulsed Doppler in 6 of 8 fetuses, all with one or multiple spleens confirmed postnatally. The splenic artery could not be imaged in two fetuses, both with asplenia confirmed postnatally. The perinatal mortality rate was 88% (7 of 8) and the one surviving infant is currently alive and well at 3 years of age. Color and pulsed Doppler of the splenic artery can aid in the prenatal diagnosis of heterotaxic syndromes. This information is of value and should result in improved prenatal counseling and management of affected pregnancies.

Bernard-Soulier syndrome in pregnancy: case report and review of the literature.

Bernard-Soulier Syndrome is a rare hereditary thrombocytopathy that manifests clinically by excessive bleeding out of proportion to the degree of thrombocytopenia. Only eight reports of Bernard-Soulier Syndrome in pregnancy have been previously described. In some patients the pregnancy course was smooth while in others post-partum haemorrhage was the most common complication. We present a primiparous female who had immediate and delayed post-partum haemorrhage that was managed conservatively. Review of the literature is also included.

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.

Immune thrombocytopenia and elemental mercury poisoning.

Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease. Each of the four children in this family were treated with dimercaptosuccinic acid. The hazard of vacuuming spilled mercury and appropriate clean-up procedures are described.

[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.

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.

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.

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.