Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF

Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are small proteins, which are related both by sequence and by in vitro enzyme activity. Here we show that the gene for DDT in human and mouse is identical in exon structure to MIF. Both genes have two introns that are located at equivalent positions, relative to a twofold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT. In addition to similarities in structure, the genes for DDT and MIF are closely linked on human Chromosome (Chr) 22 and mouse Chr 10.     

Valvular disease associated with systemic illness

The connective tissue diseases are immune-mediated inflammatory diseases that manifest predominantly with symptoms and signs of musculoskeletal and mucocutaneous inflammation. They frequently affect the heart valves, pericardium, and myocardium. In patients with AKS, the aortic root and conduction system are also frequently involved. Echocardiographic series in these patients have demonstrated that valvular disease is highly prevalent and associated with substantial morbidity and mortality (Table 1). The prevalence rates of clinically detected valvular disease, however, are either unknown or low. This discrepancy is related to lack of awareness, overshadowing of the cardiovascular manifestations by the inflammatory symptoms and signs of the musculoskeletal system, lack of systematic application of the history and cardiovascular physical examination, and high sensitivity of echocardiography for detecting subclinical abnormalities. Several valvular abnormalities have been identified as unique to a specific disease. Libman-Sacks vegetations, valve nodules, and subaortic bump are characteristic of SLE, RA, and AKS (see Table 1). The valvular complications and respective therapy are similar to those of other causes of valvular disease; however, the associated morbidity and mortality of these complications in these patients are high. The worse prognosis of valvular disease in these patients is related to the chronicity and debilitating nature of their illness, their high prevalence of multisystem disease, and immunosuppression. These factors underscore the importance of early recognition, prevention of complications, and proper clinical or echocardiographic follow-up. The distinctive echocardiographic characteristics of the valve abnormalities associated with the connective tissue diseases may allow their differentiation from other common valvulopathies, such as infective endocarditis, rheumatic valvular disease, and degenerative valvular disease (Table 2). Despite the clinical and prognostic implications of valvular disease associated with the connective tissue diseases, incomplete data are available about pathogenesis, relation to clinical features of the primary disease, evolution, and effect of steroid or cytotoxic therapy. Echocardiography, especially TEE, has the potential to redefine the prevalence rates and to characterize better the valve abnormalities associated with these conditions. Finally, future large cross-sectional and longitudinal studies using clinical and echocardiographic data may help to define better the presence, evolution, and therapy of the valvular disease associated with the connective tissue diseases.     

Acute myeloid leukemia-type chemotherapy for newly diagnosed patients without antecedent cytopenias having myelodysplastic syndrome as defined by French-American-British criteria: a Cancer and Leukemia Group B Study

PURPOSE: To determine the treatment outcome of standard acute myeloid leukemia (AML)-type chemotherapy in a subset of patients with newly diagnosed myelodysplastic syndromes (MDS) compared with that of patients with de novo AML as defined using French-American-British (FAB) criteria. In addition, to determine the pretreatment variables having prognostic significance for treatment outcome in patients with MDS. PATIENTS AND METHODS: Nine hundred seven newly diagnosed patients with no history of cytopenias having a local institutional de novo AML successfully karyotyped and treated on Cancer and Leukemia Group B (CALGB) protocols for AML from 1984 to 1992. Thirty-three of the 907 patients were reclassified as having MDS on central pathology review using FAB criteria and form the basis of this analysis. RESULTS: The treatment outcomes for patients with MDS and AML were similar; the complete remission (CR) rate was 79% and 68%, respectively (P = .37); median CR duration was 11 and 15 months, respectively (P = .28); and median survival was 13 and 16 months, respectively (P = .72). For the MDS patients, there were no prognostic variables for CR rate identified. For CR duration, only the Sanz classification had prognostic value. The prognostic factors for survival in a univariate analysis included age, WBC count, Sanz classification, and percent blood blasts. In a proportional hazards analysis of survival, age greater than 60 years and WBC less than 2.6 x 10(9)/L were adverse prognostic factors. CONCLUSION: In patients with no known history of cytopenias who are treated intensively at diagnosis, the FAB distinctions between MDS (refractory anemia with excess blasts and refractory anemia with excess blasts in transformation) and AML appear to have little therapeutic relevance.     

Recurrent meningitis in a case of congenital anterior sacral meningocele and agenesis of sacral and coccygeal vertebrae

A rare case of recurrent meningitis due to congenital anterior sacral meningocele and agenesis of the sacral and coccygeal vertebrae is described. An autosomal dominant inheritance is demonstrated for lower cord malformation, and environmental factors (chromic acid or fumes) are discussed.     

Transperineurial capillary abnormalities in the sural nerve of patients with diabetic neuropathy

Morphometric techniques were employed to assess perineurial capillary abnormalities in the sural nerve of 20 diabetic patients with neuropathy and 10 normal control subjects. Structural abnormalities were related to quantitative neurophysiological and neuropathological measures of neuropathy. Perineurial capillary endothelial cell area (P < 0.001) and endothelial cell profile number (P < 0.01) were increased and luminal area (P < 0.001) was reduced in diabetic patients when compared with control subjects. A significant relationship was observed between endothelial cell hyperplasia and measures of neuropathic severity. These findings provide evidence for perineurial capillary luminal occlusion due primarily to both endothelial cell hypertrophy and hyperplasia. Such a reduction in luminal size is expected to reduce transperineurial and hence endoneurial blood flow, resulting in endoneurial hypoxia and hence human diabetic neuropathy.     

Estrogen replacement in women treated for breast cancer

Oestrogen replacement therapy in women with a history of breast cancer has long been considered contraindicated. However, the literature does not indicate an increased risk of recurrent breast cancer in postmenopausal women receiving oestrogen replacement therapy. We advocate that women with a history of breast cancer without nodal involvement could be offered oestrogen replacement therapy and thereby benefit from prevention of cardiovascular disease and osteoporosis. But the patients must accept a potentially increased risk of recurrence. We emphasize the need for randomized prospective studies.     

Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes

OBJECTIVE: To examine the effects of vitamin E on total serum protein glycation (fructosamine), hemoglobin glycation (HbA1c), and serum levels of glucose, total cholesterol, triglycerides, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B. MATERIAL AND METHODS: Sixty poorly controlled diabetic patients were randomly assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules during a two month period following a double blind cross-over design with a four week wash-out period between regimens. RESULTS: Seven patients were excluded from the study because of reasons not related to the medication. In the remaining 53 patients, the levels of serum glucose, fructosamine, HbA1c, total cholesterol, HDL-C, LDL-C, Apo A1 and Apo B did not vary significantly with vitamin E as compared with placebo. CONCLUSIONS: No significant effects of vitamin E on any of the parameters evaluated were observed in poorly controlled diabetic patients.     

Positron emission tomography in the detection and management of metastatic melanoma

OBJECTIVE: In women who use oral contraceptives with low estrogen doses, a quiescent endometrium is frequently produced. Further reduction of the estrogen dose would not be expected to alter this effect. In this open-label study, the effects on the endometrium of a monophasic oral contraceptive containing 75 micrograms gestodene and 20 micrograms ethinylestradiol were assessed. METHOD: Biopsies were performed on 25 women on therapy. The biopsies were performed during the late luteal phase (last 7 days) in the pretreatment cycle and during days 15-21 in cycle 6 for 13 subjects (Group A) and during days 15-21 in cycle 3 and during the late luteal phase (last 7 days) in the post-treatment cycle for 12 subjects (Group B). RESULTS: All subjects completed six cycles of treatment. Nine of 13 subjects pretreatment and nine of 12 subjects at cycle 3 were characterized by the pathologist as having a secretory endometrium. Four of 13 subjects at cycle 6 and ten of 11 subjects post-treatment also demonstrated a secretory endometrium. Pre-decidual changes were seen in one, two, two and zero subjects at pretreatment, after three cycles, six cycles, and post-treatment, respectively. Six subjects had an atrophic endometrium at cycle 6. CONCLUSIONS: With monophasic gestodene/ethinylestradiol 75 micrograms/20 micrograms, a secretory or inactive endometrium was present in most subjects. Thus, the effects on the endometrium of this oral contraceptive containing a reduced estrogen dose are consistent with those produced by other low-estrogen-dose combination oral contraceptives.