The limitation of staged repair in the surgical management of congenital complex heart anomalies with aortic arch obstruction

OBJECTIVE: Severe aortic arch obstruction including an interrupted aortic arch in congenital complex heart anomalies remains a challenge in surgical management. METHODS: Treatment and outcomes in 75 consecutive patients who underwent an aortic arch repair as the first step of the staged repair protocol between 1975 and 2000 were reviewed. Their ages at repair ranged from 1 day to 8.5 months. RESULTS: Cross-sectional postoperative follow-up data were available in all the patients. The follow-up period ranged from 0 to 27.6 years (mean: 7.3 +/- 7.3 years). There were 20 postoperative hospital deaths (27%) and 7 late deaths. The Kaplan-Meier estimate of survival was 81.3% +/- 4.5% at 1 month, 68.0% +/- 5.4% at 1 year, 65.0% +/- 5.5% at 5 years, 63.1% +/- 5.7% at 10 years, 63.1% +/- 5.7% at 20 years. By Cox regression analysis, body weight of 2.5 kg or less is the only independent determinant of postoperative mortality (p = 0.04, multivariable odds ratio: 2.50, [95% confidence interval: 1.02-6.1]). The aortic arch morphology, the primary cardiac lesion, or date of operation did not reach a statistically significant level to show correlation with mortality. Reintervention to reconstruct the aortic arch was performed at 9 occasions in 8 of the 55 patients who survived the primary operation (14.5%). The Kaplan-Meier estimate of the reintervention-free rate was 91.3% +/- 4.2% at 5 years, 85.5% +/- 5.6% at 10 years, 75.6% +/- 8.2% at 20 years. Using multivariable Cox regression analysis, interrupted aortic arch (versus aortic coarctation) was the only independent predictor of a shorter time to reintervention (p = 0.001, multivariable odds ratio: 16.1, [95% confidence interval: 3.2-80.2]). CONCLUSIONS: The staged repair protocol was associated with significant limitations in patient survival and with the development of recurrent aortic arch obstruction. Thus, a primary repair protocol may serve as an alternate approach, especially in patients with low weight or with an interrupted aortic arch.     

Treatment of prolactinoma based on the results of transsphenoidal operations

Ninety-eight patients (16 male, 82 female) with prolactinomas were treated by transsphenoidal operation. The postoperative course was closely related to the tumor size and the preoperative levels of serum prolactin. In 37 (74%) of 50 patients with microadenomas, the levels of serum prolactin returned to normal postoperatively. There were 48 patients with macroadenomas; 27 of these were expansive and 21 were invasive. In 9 (33%) of the 27 patients with expansive macroadenomas, the postoperative levels of prolactin returned to normal; this was not the case in any of the 21 patients with invasive macroadenomas. Of 81 premenopausal women, 35 (43%) resumed normal menstruation postoperatively. All patients with preoperative deficits in the visual field experienced postoperative improvement. There were no postoperative deaths or serious complications in this series. Our data indicate that microprolactinomas are highly curable by transsphenoidal operation alone. In women who plan to have children, prolactinomas should be removed immediately. On the other hand, in patients with macroprolactinomas who manifest high levels of serum prolactin, initial treatment with bromocriptine should be considered because there is little hope for surgical cure and postoperative bromocriptine treatment might be necessary.     

Decreased erythrocyte delta-aminolevulinate dehydratase activity after styrene exposure

delta-Aminolevulinate dehydratase (ALA-D:porphobilinogen synthase, 5-aminolevulinate hydro-lyase, EC 4.2.1.24) activity was depressed markedly in red cells of rats exposed to 0.21 g/m3 styrene, a chemical widely used in commercial products. The depression was not restored in vitro after treatment with dithiothreitol and zinc. Consistent with this finding, radioimmunoassay of the enzyme protein demonstrated reduction in the enzyme concentration by styrene exposure. There was a good correlation between the decrease in enzyme activity and its concentration in the styrene-treated animals, suggesting that the depression of the enzyme activity was essentially due to the reduction in the enzyme content. Decrease in the enzyme content in bone marrow cells to almost the same extent as that in erythrocytes seems to indicate the decreased synthesis of ALA-D in the bone marrow. In vitro studies showed that styrene 7,8-oxide, the major intermediate of styrene metabolism, decreased the activity of purified ALA-D but that styrene, the parent compound itself, had no inhibitory effect. The activity and concentration of erythrocyte ALA-D in workers chronically exposed to styrene were also depressed significantly. These findings indicate that the styrene exposure-mediated decrease of ALA-D activity in erythrocytes was a reflection of reduction in the enzyme protein, which may have been the result of styrene 7,8-oxide action, and they suggest that a similar process may also be involved in the reduction of erythrocyte ALA-D in styrene-exposed workers.     

Prediction of spinal cord ischemia with a retrievable stent graft on endovascular treatment for a case of thoracic aortic aneurysm

Multiple aortic aneurysms in Behçet’s disease were repaired with transluminaly placed endovascular stent grafts. Before deploying the stent graft device for permanent implantation for the saccular aneurysm located in the descending thoracic arota, from which feeding arteries for the spinal cord possibly branched, a retrievable stent graft was inserted and evoked spinal cord potential (ESP) were monitored in order to predict spinal cord ischemia. The original retrievable stent graft, constructed of a self-expandable Z-shaped stainless steel stent covered with e-PTFE, can be easily withdrawn into a 18 Fr. sheath after deployment. Blood flow into intercostal arteries branching from that part of the descending aorta where the permanent stent graft is planned to be implanted, is intercepted by the retrievable stent graft. A change of ESP during the temporary implantation of the device indicates that spinal cord ischemia would be caused by permanent implantation of the stent graft. In this case, no change of ESP was observed and the patient showed no postoperative paraplegia.The retrievable stent graft was useful for prediction of spinal cord ischemia before endoluminal stent graft repair of the descending aortic aneurysm. However, the device is not flexible enough to fit a severely tortuous aorta, therefore we are obliged to select patients to some extent. Further improvement of the device is required to make prediction of spinal cord ischemia with the retrievable stent graft possible in all cases.     

Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.     

Circadian rhythm and stress in the elderly: a study using salivary cortisol levels as an indicator

Biological response to stress was studied in the healthy elderly by fluctuations of their circadian rhythms using salivary cortisol levels as an indicator. Social activities per se may not be stressors, but may serve as a "eustress" to the elderly when they are in good health because their rhythm is maintained. Concerning the occupations of the subjects, the rhythms of elderly watchmen showed no disturbance when they slept for three hours between 23:00 and 2:00. However, those who were unable to sleep showed disturbed rhythms. We concluded that disturbance of a rhythm that has been established on the basis of being active during the day time and sleeping at night could be a stressor to the elderly rather than stress due to working as a guard.     

Preparation of 67Ga-labeled antibodies using deferoxamine as a bifunctional chelate. An improved method

Radionuclides or anti-cancer drugs may be coupled to antibodies for specific transport to target tissues. We have previously reported that several proteins could be rapidly and efficiently labeled with gallium (67Ga) by using deferoxamine (DFO) as a bifunctional chelating agent. In the present paper, we have described the use of hetero-bifunctional agents for the conjugation of DFO with antibodies and investigated the effect of coupling agents on in vitro properties and biodistribution of 67Ga-labeled antibodies. 67Ga-labeled monoclonal antibodies retained antigen-binding activity when prepared under optimum conditions. The use of hetero-bifunctional reagents, such as succinimidyl 6-maleimido-hexanoate (EMCS) or N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), which link thioether bonds and disulfide bridges prevented the formation of polymerized antibodies. Although high non-specific uptake in the liver was observed with radiolabels prepared by the homo-bifunctional agent glutaraldehyde, uptake in the liver was low with conjugates linked by hetero-bifunctional agents. 67Ga-labeled antibodies with thioether bonds showed in vivo stability, but the clearance from the circulation was the fastest with the radiolabel holding disulfide bonds. The coupling reagents used to link DFO and antibodies greatly influenced both in vitro properties and in vivo distribution of labeled antibodies and 67Ga-labeled antibodies provide a good model for the study of coupling methods and biodistribution of antibody conjugates.     

Amino acid residues conferring the nucleotide binding properties of N-acetyl-D-glucosamine 2-epimerase (renin binding protein)

Our recent studies have demonstrated that the middle domain of N-acetyl-D-glucosamine (GlcNAc) 2-epimerase participates in the specificity for and binding of nucleotides. To identify the residue conferring nucleotide binding, amino acid substitutions were introduced in the human and rat GlcNAc 2-epimerases. The mutational analyses indicate that residue 171 of GlcNAc 2-epimerase is critical for the nucleotide binding of GlcNAc 2-epimerase.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.