Laotian (delta beta) degree-thalassemia: molecular characterization of a novel deletion associated with increased production of fetal hemoglobin

We have identified and molecularly characterized a novel deletion in the beta-globin gene cluster that increases fetal hemoglobin (HbF) synthesis in a 24-year-old Laotian man who is heterozygous for this mutation. The patient is asymptomatic with a mild anemia, hypochromia, and microcytosis (Ht = 39%, MCH = 22.8 pg, MCV = 71 fl), normal levels of HbA2 (3.0%) and 11.5% HbF (G gamma A gamma ratio 60 to 40), with heterocellular distribution (52% F cells). Extensive restriction endonuclease mapping defined the 5' breakpoint within the IVS II of the delta-globin gene, between positions 775 to 781 very similar to the 5' breakpoint of the Sicilian delta beta-thalassemia. However, the 3' breakpoint was localized between two Pst I sites 4.7 kb 3' of the beta- globin gene, thus ending about 0.7 kb upstream from the 3' breakpoint of the Sicilian delta beta-thalassemia. This results in a 12.5 kb deletion of DNA. It is of interest that the 5' breakpoint of the deletion residues within an AT-rich region which has been proposed as a specific recognition signal for recombination events, while the 3' breakpoint lies within a cluster of L1 repetitive sequences (formerly known as Kpn I family repeats). The presence of the 3' breakpoints of several other deletions within this region of L1 repeats also suggests that such sequences might serve as hot spots for recombination and eventually lead to thalassemia deletions. The similarity of the 5' and 3' breakpoints of these delta beta-thalassemias underscores the putative regulatory role of the deleted and juxtaposed sequences on the expression of the gamma-globin genes in adult life.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.     

The Utility of a Dilatation and Evacuation Procedure in Patients with Symptoms Suggestive of Ectopic Pregnancy and Indeterminate Transvaginal Ultrasonography

OBJECTIVES: To ascertain the overall frequency of obtaining chorionic villi (CV) in patients with indeterminate transvaginal ultrasound (US) examinations who have had a dilatation and evacuation (D+E) procedure performed, to determine whether the frequency of obtaining CV is dependent on whether the endometrial cavity is empty at US, and to determine the likelihood of ectopic pregnancy in patients without CV after D+E and with or without an empty endometrial cavity at US. METHODS: A retrospective review was made of consecutive ED patients presenting to an urban teaching hospital from August 1991 through August 1997 with abdominal pain or vaginal bleeding and a positive beta-human chorionic gonatropin (beta-hCG) test. Patients who had a transvaginal US that was read as indeterminate (no extrauterine findings of ectopic pregnancy, and no intrauterine fetal pole or yolk sac) and who had a D+E performed within 48 hours of the ED visit were eligible. US exams were subdivided into two groups, those with empty endometrial cavities and those with endometrial cavities that contained fluid, echogenic material, or sac-like structures. The presence or absence of CV was based on the official pathology report. Patients were excluded if pathology results were not available. RESULTS: A total of 255 patients met eligibility criteria. Of these, pathology results were not available for five patients. Of the remaining patients, 177 of 250 (70.8%: 95% CI = 64.7% to 76.3%) had CV identified in the pathology specimen. The difference in the frequencies of obtaining CV in those with empty endometrial cavities (35/78; 44.9%: 95% CI = 34% to 56%) vs. those without empty endometrial cavities (142/172; 82.6%: 95% CI = 76% to 88%) was significant (p<0.001). Ectopic pregnancy was diagnosed in 17 of 42 (40.0%) with empty uteri at US and no CV at pathology vs 5 of 26 (19.2%) in whom the uterus was not empty and no CV were obtained (p = 0.07). CONCLUSION: In symptomatic patients with indeterminate transvaginal ultrasound exams, CV will be identified after D+E in approximately 70% of cases. Although CV were found with increased frequency when the endometrial cavity was not empty, still almost half of the patients with empty uteri had villi identified. Finally, although the frequency of ectopic pregnancy was higher in the patients with empty uteri and no CV at D+E, vs. those without an empty uterus and no CV, this difference did not reach statistical significance.