Pharmacokinetic analysis of antibody localization in human colon cancer: Comparison with immunoscintigraphy

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.     

CT and MR findings in diastematomyelia, with embryogenetic consideration.

Diastemstomyelia is an extremely rare disorder that is seldom found among the Japanese. This paper presents two Japanese patients, a newborn male and a newborn female, with diastematomyelia. CT demonstrated bony spurs more clearly than plain film, and magnetic resonance images indicated split cords and associated anomalies. Although the embryogenesis of diastematomyelia has not been clearly elucidated, the coincidence of levels of associated anomalies and diastematomyelia in our cases and in the literature supports Bremer's embryogenetic explanation of persistent accessory neurenteric canal.     

DIURNAL RHYTHM OF SERUM gM-SEMINOPROTEIN IN PATIENTS WITH UNTREATED PROSTATE CANCER: COMPARISON OF THE ORIGINAL AND REVISED ASSAY KITS

To compare levels of y-seminoprotein (gM-Sm) assayed by original and revised assay systems, blood was obtained every 4 h over a 32-h period from 8 untreated prostate cancer patients. Serum levels of prostate specific antigen (PSA) were also examined. In 6 patients, the coefficient of variation (CV) of the serum levels assayed by the revised assay was significantly different from that of the intra-assay samples. In contrast, the CV of the gM-Sm serum levels assayed by the original assay differed significantly from that of the intra-assay samples in only 2 patients. The fluctuations in gM-Sm assayed by the revised assay were, at least in part, similar to those of the PSA serum levels in all patients. The mean CV of the gM-Sm serum levels assayed by the revised assay was significantly larger than that for levels measured by the original assay. After treatment, the rate of decrease in gM-Sm serum levels determined by the original assay differed from that in the serum levels of PSA and prostatic acid phosphatase. These results indicate that the original assay for gM-Sm do not detect diurnal differences in serum gM-Sm levels, even at levels below 20 ng/ml. These observations indicate that the analysis of data obtained using the original gM-Sm kit should be interpreted with caution.     

CROMAKALIM SUPPRESSES HYPERTONIC SALINE-INDUCED RENAL VASOCONSTRICTION IN ANAESTHETIZED DOGS

1. Intrarenal arterial infusion of hypertonic saline (HS) transiently increased and then gradually reduced renal blood flow (RBF) in anaesthetized dogs. Glomerular filtration rate (GFR) but not filtration fraction decreased at the end of the infusion. 2. In the presence of a potassium channel opener cromakalim (0.3 μg/kg per min), HS infusion failed to reduce RBF; the initial increase in RBF was maintained throughout the infusion. Since cromakalim also prevented the decrease in GFR, HS infusion lowered filtration fraction. 3. The results suggest that cromakalim inhibits both pre-and postglomerular vasoconstriction induced by HS infusion.     

Myocardial perfusion in patients with left bundle branch block and without coronary artery disease]

For the evaluation of myocardial perfusion in patients with left bundle branch block (LBBB), we performed exercise stress (Ex)-redistribution (RD) myocardial tomography with thallium-201 (201Tl) in 23 patients with LBBB and without coronary artery disease (CAD). Myocardial images in patients with LBBB were compared with those of 9 patients with CAD who showed Ex induced transient septal defect. Bull'-eye maps (201Tl distribution maps at Ex and RD and 201Tl washout rate [WOR] map) were made from myocardial tomograms. In 23 patients with LBBB, 15 patients (65%) developed myocardial perfusion abnormality. In 10 (67%) of these 15 patients, transient perfusion defect appeared in the entire septum (diffuse type). On the other hand in 5 patients (33%), localized fixed perfusion defect developed at the boundary between septum and anterior wall (focal type). In focal type, every patient had other disease such as hypertension, aortic stenosis or sick sinus syndrome. While in patients with diffuse type, other diseases were observed in 30% (p less than 0.05) and they were limited to hypertension or diabetes mellitus. These facts suggested that mechanisms of perfusion abnormalities might be different between these two groups. We compared the perfusion abnormality between LBBB diffuse type and CAD. The extent of the defects was not different between two groups. Although apex was included within the defect in 89% of CAD population, apical defect was observed in only 20% of diffuse type (p less than 0.05). Minimal 201Tl WOR and 201Tl uptake ratio of septum to lateral wall indicated that exercise induced septal defect was slighter in diffuse type than CAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Excessive rapid palatal expansion with Latham appliance for distal repositioning of protruded premaxilla in bilateral cleft lip and alveolus.

OBJECTIVE: This article reports a case of bilateral cleft lip and alveolus (BCLA) for which excessive rapid palatal expansion with a Latham appliance was performed for preoperative alignment of the protruded premaxilla. Postoperative changes of maxillary width were investigated with serial plaster casts. PATIENT AND RESULTS: A 3-month-old girl presented with complete BCLA in which the premaxilla was markedly protruded. Preoperative alignment of the protruded premaxilla with a Latham appliance was planned to facilitate primary lip repair. The appliance was placed when the patient was 4.5 months old. The necessary palatal expansion was estimated to be 7.0 mm in order to move the premaxilla backward into the ideal position. After palatal expansion and posterior repositioning of the protruded premaxilla, the primary operation, including cheiloplasty and gingivoperiosteoplasty, was performed when the patient was 7 months old. Excessive maxillary expansion might be a cause of transverse maxillomandibular discrepancy. Measurement with serial plaster casts demonstrated that maxillary widths increased from 42.3 mm pretreatment to 49.0 mm after orthopedic treatment but relapsed markedly to 43.5 mm at 3 months after the primary operation. Therefore, the net change of maxillary widths was only 1.2 mm. After alignment of the protruded premaxilla, tension-free soft tissue repairs were performed, and a harmonious alveolar arch was obtained without change in maxillary width. CONCLUSION: These results indicate that this method is useful for preoperative management of BCLA with protruded premaxilla.     

Human monocyte antigens in a random sample from Japan.

We studied a random sample of Japanese and compared both Japanese and German monocyte antigen frequencies and performed a segregation analysis in Japanese families. In Japanese, the following gene frequencies were established: 0.1033 for HMA-A1; 0.0299 for HMA-A3; 0.0033 for HMA-A6; 0.1521 for HMA-B2. Data on the gene frequency in Germans were presented by Rose. In this comparison, the frequency for HMA-B2 in Japanese is more than two times higher; for antigen HMA-A6, the Japanese is a fifth of the German quantity. The antigen HMA-B4 was not found in Japanese. The results we obtained from family analysis confirmed an unambiguous autosomal, codominant inheritance of the examined HMA antigens.     

Respiratory symptoms and cigarette smoking in 3,197 pulmonologist-based asthmatic patients with a highly prevalent use of inhaled corticosteroid.

The relation between smoking and risk of asthma has been well-examined; however little attention has been paid to the correlation between smoking and asthma symptoms. The aims of this study were to examine respiratory symptoms in asthmatics with a highly prevalent use of inhaled corticosteroid (ICS) and to assess the effects of smoking and its cessation. A cross-sectional study of pulmonologist-based 3197 asthmatics (men 45.2%, ages 20-97) was performed using a questionnaire about smoking habits, the incidence and frequency of symptoms (sputum, cough and wheezing, night symptoms, and shortness of breath), physical activity interference, and medication. Although 81.4% of the patients used ICS according to the international guideline, 14.9% had activity interference, and daily symptoms remained in 43.3%. At the time of the questionnaire, 21.6% were current and 25.1% were ex-smokers. In multiple logistic regression analysis, the factors of significance (p < 0.0001) were (1) smoking; for all four symptoms, (2) age and duration of asthma; for shortness of breath. Current smokers were at a risk of sputum (age-adjusted odds ratio 2.32 [95% confidence interval 1.73-3.11]; 2.09 [1.57-2.79]), of cough and wheezing (2.38 [1.81-3.14]; 1.78 [1.35-2.36]), of night symptoms (1.95 [1.41-2.60]; 1.47 [1.09-1.98]), and of shortness of breath (1.70 [1.26-2.28]; 1.30 [0.97-1.75]) in men and women, respectively. These ratios in ex-smokers decreased to the level similar to nonsmokers. Although 81.4% of asthmatic patients used ICS, 43.3% complained of daily respiratory symptoms, especially sputum. It is suggested that the effects of ICS on asthma symptoms may be interfered with by smoking and therefore more emphasis should be placed on cessation of smoking.