Suppressive Therapy for Radiation-Associated Nodular Thyroid Disease: Double-Blind Study With T3 and Desiccated Thyroid

A thyroid screening program for individuals who had irradiationto the head and neck areas was started at Roswell Park MemorialInstitute in February 1977 and by June 1979, 1,071 patientswere seen in the clinic. Three hundred and ninety-six patientswere found to have palpable abnormalities of the thyroid, andfollowing pretreatment evaluation, suppressive therapy withtriiodothyronine (T3) (50 µ/day) or DT (desiccated thyroid)(1 20 mg/day) was administered in a double-blind fashion. Twohundred fifty patients with nodular disease completed 6 mo oftreatment and are analyzed in this paper. Pretreatment thyroidfunction tests showed that two patients had hypothyroidism witha high thyroid-stimulating hormone (TSH) and a low thyroxinelevel. A high incidence of thyroid autoantibodies was also notedand surgical findings confirmed a high incidence of chronicthyroiditis. Complete disappearance of the nodules was seenin 29% of the patients, and in addition, 38% of the patientswere seen to have significant shrinkage of the nodules, indicatingthat radiation-associated thyroid nodules were as sensitiveto the thyroactive agents as nonirradiated nodular thyroid disease.There was little difference in the response rate between T3and DT. Both agents suppressed circulating TSH levels to anunmeasurable level in 76% of the patients. There was no correlationbetween scan findings and response rates. Thyroid carcinomawas found in 19% of the patients who underwent surgery; althoughall were well-differentiated carcinomas, two-thirds of the patientsalready had evidence of dissemination and/or invasion suggestingthe aggressive nature of postirradiation thyroid carcinoma.     

Anti-β 2 -Glycoprotein I Autoantibodies and Atherosclerosis

β-Glycoprotein I (β 2 -GPI) is a major antigen for antiphospholipid antibodies (aPL) present in patients with antiphospholipid syndrome (APS). We previously reported that β 2 -GPI specifically binds to oxidized low-density lipoprotein (oxLDL). Further, a ligand specific for β 2 -GPI, oxLig-1, purified from the extracted lipids of oxLDL was identified as 7-ketocholesterol-9-carboxynonanoate (i.e., 9-oxo-9-(7-ketocholest-5-en-3β-yloxy) nonanoic acid) OxLig-1 was recognized by β 2 -GPI and subsequently by anti-&beta 2 -GPI autoantibodies. Binding of liposomes containing oxLig-1 to macrophages were significantly enhanced in the presence of both β 2 -GPI and an anti-β 2 -GPI autoantibody derived from (NZW×BXSB) F1 mouse, an animal APS model, or from APS patients. Anti-β 2 -GPI autoantibodies derived from APS patients with episodes of arterial thrombosis were detected in ELISA, using a solid phase &beta 2 -GPI complex with oxLig-1. It was also reported that LDL-receptor-deficient mice that were fed a chow diet and immunized with β 2 -GPI had an accelerated atherosclerosis and that β 2 -GPI was abundantly expressed within subendothelial regions and intimal-medial borders of human atherosclerotic plaques. All of these observations strongly suggest that autoimmune atherogenesis linked to β 2 -GPI interaction with oxLDL and autoantibodies may be present in APS.     

Bepridil Prevents Paroxysmal Atrial Fibrillation by a Class III Antiarrhythmic Drug Effect

YOSHIDA, T., et al .: Bepridil Prevents Paroxysmal Atrial Fibrillation by a Class III Antiarrhythmic Drug Effect. Background: Bepridil, a multiple ion-channel blocker, has been reported to prevent paroxysmal atrial fibrillation (PAF). The f-f interval of PAF during treatment with bepridil versus class Ic antiarrhythmic drugs was compared. Methods: Fifty-two patients with PAF were randomized to bepridil, 200 mg/day   (n = 14)   versus flecainide, 100 to 200 mg/day   (n = 15)   or pilsicainide, 75 to 150 mg/day  ( n = 23)   . The drug was considered effective when symptomatic episodes of PAF were decreased to < 50% during a follow-up of 2 to 6 months. The f-f interval was measured in 12-lead ECGs of initial PAF episodes. Results: Bepridil and Ic were effective in 10 of 14 (71.4%) and 24 of 38 patients (63.2%), respectively (ns). In the Ic group, the f-f interval was longer in successfully   (114 ± 48  ms)   than in unsuccessfully   (68 ± 25  ms)   treated patients   (P = 0.002)   . In the bepridil group, the f-f interval was shorter in successfully   (84 ± 27  ms)   than unsuccessfully   (155 ± 68  ms)   treated patients   (P = 0.015)   . When comparing unsuccessfully treated patients, the f-f interval in the bepridil group was significantly longer than in the Ic group   (P = 0.007)   . Conclusions: Bepridil was as effective as Ic drugs in the prevention of PAF. Because it was more effective in smaller (functional) than larger (anatomical) reentrant circuits, the effect of bepridil was considered to be mainly attributable to a class III antiarrhythmic action. (PACE 2003; 26[Pt. II]:314–317)     

Rat Yolk Sac Tumor: Biological Aspects and Microheterogeneity of AFP

α-Fetoprotein (AFP)-producing yolk sac tumors were established in rats as transplantable tumor lines growing in either solid or ascitic form. AFP levels in the ascites and in the serum of recipients were quite high, but higher in castrated female rats than male rats. The tumor cells were cultured also in vitro and showed synthesis of AFP and albumin. AFP produced by the yolk sac tumors was investigated comparatively with AFP produced by a hepatoma. There was no remarkable difference between two AFPs in behavior in gel filtration; however, AFP of yolk sac tumors migrated more slowly than that of hepatoma in immunoelectrophoresis. However, the mobilities of two AFP preparations became same after desialization by neuraminidase treatment. This fact suggests that AFP of yolk sac tumors contains sialic acids in smaller amount than that of hepatomas.     

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.     

Impaired monocyte differentiation in children with acute lymphoblastic leukaemia: its evaluation by peroxidase activity and ultrastructure

The ability of monocyte differentiation in childhood acute lymphoblastic leukaemia (ALL) was evaluated on the basis of the ultrastructure and peroxidase (PO) activity which could show the differentiation of cultured monocytes. In the control, PO activity limited to the granules decreased time-dependently during culture for 4 d, and was closely associated with the morphological development to macrophages. In childhood ALL, monocytes showed poor changes in both PO activity and morphological features during culture for 4 d compared to the control. Therefore, we conclude that monocyte to macrophage differentiation is impaired in childhood ALL.     

Phase I and Preliminary Phase II Studies on Aclacinomycin A in Patients with Acute Leukemia

Eight patients with acute nonlymphocytic leukemia (ANLL) andfive patients with acute lymphocytic leukemia were treated withaclacinomycin A. It was given daily by one-hour infusion indoses ranging from 0.33 to 0.70 mg/kg for seven to 20 days withoutother antileukemic agents. Two patients with ANLL achieved completeremission and one with ANLL achieved partial remission. Itsmajor toxic effects were myelosuppression and gastrointestinalsymptoms.