Thyroid hormone resistance. Clinical, biochemical and genetic study of a family

OBJECTIVE: To investigate the incidence rate of IDDM in China. RESEARCH DESIGN AND METHODS: The Chinese IDDM registry was established in 1991 as part of the World Health Organization's Multinational Project for Childhood Diabetes (DiaMond) project. Twenty-two centers were developed to monitor the incidence of IDDM in children < 15 years of age. The population under investigation includes > 20 million individuals, representing approximately 7% of the children in China. Capture-recapture methods were used to estimate the ascertainment. RESULTS: The overall ascertainment-corrected IDDM incidence rate in China was 0.51 per 100,000, the lowest rate ever reported. There was a 12-fold geographic variation (0.13-1.61 per 100,000). In general, the incidence rate was higher in the north and the east. There was a sixfold difference among ethnic groups (highest: Mongol group, 1.82 per 100,000; lowest: Zhuang group, 0.32 per 100,000). CONCLUSIONS: China has an extremely low overall IDDM incidence rate. China also has the greatest geographic and ethnic variation seen for any country.     

Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development

The production, survival and function of monocytes and macrophages are regulated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor Fms. Binding of M-CSF results in Fms autophosphorylation on specific tyrosines that act as docking sites for intracellular signaling molecules containing SH2 domains. Using a yeast two-hybrid screen, we cloned a novel adaptor protein which we called 'Mona' for monocytic adaptor. Mona contains one SH2 domain and two SH3 domains related to the Grb2 adaptor. Accordingly, Mona interacts with activated Fms on phosphorylated Tyr697, which is also the Grb2-binding site. Furthermore, Mona contains a unique proline-rich region located between the SH2 domain and the C-terminal SH3 domain, and is apparently devoid of any catalytic domain. Mona expression is restricted to two hematopoietic tissues: the spleen and the peripheral blood mononuclear cells, and is induced rapidly during monocytic differentiation of the myeloid NFS-60 cell line in response to M-CSF. Strikingly, overexpression of Mona in bone marrow cells results in strong reduction of M-CSF-dependent macrophage production in vitro. Taken together, our results suggest an important role for Mona in the regulation of monocyte/macrophage development as controlled by M-CSF.     

Mitral valve replacement with the St. Jude Medical prosthesis: a 15-year follow-up

BACKGROUND: A retrospective study was conducted to analyze the results of St. Jude Medical mitral valve replacement. METHODS: From January 1979 to December 1989, 870 patients (54% women, 46% men; mean age, 55.8 +/- 6.2 years) underwent mitral valve replacement with the St. Jude Medical prosthesis. Of these operations 616 were isolated mitral valve replacements and 254 were double valve replacements. Coronary artery bypass grafting was performed concomitantly in 55 patients (6.3%). RESULTS: Overall, early mortality was 5.05%, with 4.2% for the isolated mitral valve procedure and 7.08% for the double valve replacement. Follow-up at 15 years was complete in 859 patients (98.74%). Mean follow-up time was 93.5 months, for a total of 6,436 years. Actuarial survival at 15 years was 59.5% +/- 5%, 60.5% +/- 6%, and 56.9% +/- 9%, for the entire group, the isolated mitral valve and double valve procedures, respectively. Multivariate analysis identified age, sex, hospital stay, and preoperative mitral regurgitation as independent prognosis factors for overall mortality. Of 606 patients alive at the latest follow-up, the New York Heart Association class improved significantly (from 67% class III/IV before the operation to 88% class I/II after the operation). All patients received warfarin to maintain an international normalized ratio between 3.5 and 4. The linearized rates (% per patient-year) of thrombosis, thromboembolism, and major hemorrhage were, respectively, 0.21, 0.75, and 0.94 for the entire group; 0.18, 0.67, and 0.88 for the isolated mitral valve operation; and 0.15, 0.92, and 1.08 for the double valve replacement. For the entire group the freedom from thrombosis and thromboembolism at 15 years was 98.1% +/- 1% and 88% +/- 4%, respectively. No case of structural dysfunction occurred. The freedom from paravalvular leak and endocarditis at 15 years was 95.3% +/- 2% and 97.3% +/- 2.4%, respectively. The probability of remaining free from reoperation at 15 years was therefore 95.6% +/- 2.5%. CONCLUSIONS: These results confirm that the St. Jude Medical valve is a reliable prosthesis with very low thrombosis and thromboembolism rates, allowing the use of a low dose of anticoagulation with an international normalized ratio of about 3.     

Pheochromocytoma

We present a series of 11 patients with pheochromozytomas. We recommend screening for a catecholamine-producing tumor for every patient with hypertension. Screening and diagnosis are based on demonstration of an increased catecholamine production or -excretion. In our laboratory determination of urinary vanillin-mandelic-acid proved to be quite accurate. As 6 of our 11 pheochromozytomas were found extra-adrenally preoperative evaluation with regard to localization of these tumors appears as sound practice. According to our experience no single examination can be favoured. Therefore localization of these tumors is best accomplished by multiple diagnostic procedures. Morbidity and mortality depend directly upon preoperative recognition of a catecholamine-producing tumor and thus according management. We were able to gather data on 8 of 10 surviving patients 4--13 years postoperatively. Six of these are normotensive without any treatment.     

A highly sensitive C-terminal specific radioimmunoassay for human parathormone as a routine method (author's transl)

The basis for the radioimmunoassay of parathormone (PTH) as a routine method is a new sheep antiserum and a labelled PTH stabilised by a modification of the purification technique. The antiserum is obtained by immunisation with pig and cattle parathormone, it is C-terminal specific and is used in the assay in a final dilution of 1:35000. The affinity to human PTH is markedly greater than of the antisera used up to now. Two purification steps of 125J labelled bovine PTH lead to a tracer with a nonspecific binding of approximately 5% which increases to approximately 10% within 6 weeks. All normal sera investigated so far were measurable quantitatively (normal range 0.7 to 2.5 mul/equiv.). The lower sensitivity range was at 0.3 mul/equiv. All patients with chronic renal insufficiency and dialysis patients have an increased PTH concentration (3.9 to greater than 20 mul/equiv.). This also applies to patients with primary hyperparathyroidism (2.9 to greater than 20 mul/equiv.).