Raising awareness of carrier testing for hereditary haemoglobinopathies in high-risk ethnic groups in the Netherlands: a pilot study among the general public and primary care providers

Background  

In the Netherlands no formal recommendations exist concerning preconceptional or antenatal testing for carriership of hereditary haemoglobinopathies. Those at highest risk may be unaware of the possibility of carrier screening. While universal newborn screening has recently been introduced, neither preconceptional nor antenatal carrier testing is routinely offered by health care services to the general public. A municipal health service and a foundation for public information on medical genetics undertook a pilot project with the aim of increasing knowledge and encouraging informed choice. Two groups were targeted: members of the public from ethnic groups at increased risk, and primary health care providers. This study examines the effectiveness of culturally specific 'infotainment' to inform high-risk ethnic groups about their increased risk for haemoglobinopathies. In addition, the study explores attitudes and intentions of primary care providers towards haemoglobinopathy carrier testing of their patients from high-risk ethnic groups.     

Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations

Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated serum IgE, and a variety of connective tissue and skeletal abnormalities. Individuals with HIES share a characteristic facial appearance and many oral manifestations including retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis. Mutations in STAT3 account for the majority, if not all, of the cases of autosomal dominant HIES, but the pathogenesis of the many varied features remains poorly understood. In this review, we discuss the clinical phenotype of HIES including immunologic and non-immunologic features, the genetics of HIES, and treatment.     

Gastric ulcer localization by direct in vivo labeling of sucralfate. Work in progress

We developed and evaluated a new procedure for imaging gastric ulcer disease with technetium 99m-labeled sucralfate. The new method employs direct in vivo labeling of sucralfate instead of in vitro labeling using human serum albumin, as previously reported in the literature. Tests using hydrochloric acid and a rabbit ulcer model showed the efficacy of the direct in vivo labeling technique and the ability of the tagged material to bind to ulcers, respectively. In 26 studies using humans with sucralfate labeled directly in vivo, 15 gave true-negative results and 11 gave true-positive results. Of 14 studies using humans with in vitro labeled sucralfate, three gave true-negative results, three gave true-positive results, and the results of eight were either false-negative or could not be interpreted because of high levels of activity remaining in the stomach. We suggest that the direct in vivo labeling method significantly improves the sucralfate gastric ulcer imaging technique.     

Tandem autologous-allogeneic nonmyeloablative sibling transplantation in relapsed follicular lymphoma leads to impressive progression-free survival with minimal toxicity

Autologous stem cell transplantation (ASCT) prolongs survival in patients with relapsed follicular lymphoma. ASCT is usually not curative, however. Myeloablative allogeneic transplantation has produced long-term survival at a cost of significant transplantation-related mortality (TRM), whereas reduced-intensity transplantation entails less TRM but has a higher relapse rate. We thus initiated a protocol consisting of ASCT followed by nonmyeloablative allogeneic transplantation (NMT) for relapsed follicular lymphoma to mimic myeloablative allogeneic transplantation without the associated toxicity. The NMT was non-T cell-depleted, and all donors were HLA-identical siblings. We report results in 27 patients with a median age of 49 years (range, 34-65 years). Five patients demonstrated histological progression toward an aggressive lymphoma. The patients had received a median of 3 lines of previous therapy. Disease status before ASCT included 8 patients in complete remission, 14 in partial remission, and 5 refractory. Five patients developed grade II-IV acute graft-versus-host disease, and 20 patients developed chronic graft-versus-host disease requiring systemic therapy. With a median follow-up of 39 months after NMT, overall survival and progression-free survival were 96% at 3 years. We conclude that the combined ASCT-NMT strategy appears to be safe, with excellent progression-free survival even in refractory and transformed cases. This novel approach warrants further investigation in larger prospective studies.     

Ontogeny of gonadotrophin and inhibin secretion in normal girls through puberty based on overnight serial sampling and a comparison with normal boys

We measured luteinizing hormone (LH) and follicle stimulating hormone (FSH) by immunofluorometric assays and alpha-inhibin by radioimmunoassay in serum sampled every 10 min throughout the night (2100-0500 h) from 44 normal girls. Mean overnight LH values rose log- linearly from a mean of 0.2 IU/l in prepubertal girls to 3.0 IU/l in late pubertal girls. Log2 mean overnight FSH rose rapidly through early puberty and then remained constant; mean FSH rose from 1.0 IU/l in prepubertal girls to approximately 2.8 IU/l in Tanner III-V girls. Mean overnight inhibin increased through puberty, rising from 151 ng/l in prepubertal girls to 432 ng/l in fully pubescent girls. Within each of the first three Tanner stages, LH differed approximately 100-fold between the smallest and largest mean concentrations but differed <10- fold within stages IV or V. Such within-pubertal stage variability was less pronounced for FSH, which differed approximately 16-fold among Tanner I subjects and 4-10-fold at later stages, and for inhibin, which varied approximately 4-fold within each Tanner stage. The frequency of LH pulses during overnight sampling increased significantly during puberty, but the frequency of FSH and inhibin pulses remained constant. We compared the results from girls to those from 50 normal boys [Manasco et al. (1995) J. Clin. Endocrinol. Metab., 80, 20462052]. At each pubertal stage, girls had approximately the same mean overnight LH values as boys; girls had higher mean overnight FSH, particularly during Tanner stages II-IV; and boys had mean overnight alpha-inhibin immunoreactivity approximately 1.5 times that of girls at each pubertal stage. Still, hormone concentrations for individuals of both sexes intergraded at each pubertal stage.