The origin and development of the upper lateral incisor and premaxilla in normal and cleft lip/palate monkeys induced with cyclophosphamide.

OBJECTIVE: Cleft lip/palate (CLP) is a common human congenital defect in which the maxillary lateral incisors are often absent, malformed, and malpositioned. The present study was designed to examine the origin of the upper primary lateral incisor relative to the medial nasal process (MNP) and maxillary process (MP) fusion area and to the premaxillary/maxillary (incisive) suture in monkeys. METHOD: Scanning electron microscopy, histology, skeletal staining, and drying techniques were used to study facial development in embryo and fetal monkey specimens. A teratogenic dose of cyclophosphamide was administered to pregnant monkeys prior to fusion of the MNP and MP and fetuses were examined for CLP. RESULTS: Formation of the anterior maxilla involved fusion of the MNP and MP at stages 14-18. At stages 18-20, the palatal portion of the MNP had formed the medial and lateral incisive mounds. By stage 22, the upper primary lateral incisor has formed within the MP, lateral to the MNP/MP fusion area and to the ossifying premaxilla. Ossification of the premaxilla begins in the MNP and subsequently spreads laterally across the MNP/MP fusion area into the MP. Accordingly, the lateral incisor undergoes a complex positional shift (mainly medial) relative to the incisive suture both prenatally and postnatally and is finally located medial to the suture. Examination of the cyclophosphamide-induced CLP fetuses showed that the lateral incisor is located lateral to the alveolar cleft and does not shift medial to the incisive suture. CONCLUSION: Understanding the origin of the lateral incisor (the tooth closest to the cleft) and the shift after its formation provides clues to high incidence of malformations and ectopia of this incisor in cleft patients.

Pharmacokinetic studies of norethisterone-3-oxime and norethisterone-3-oxime acetate in rhesus monkey.

After [6,7-3H]-labelled norethisterone-3-oxime (NETO) and norethisterone-3-oxime acetate (NETO-AC) were given intravenously or orally through a nasal tube with 1 mg of respective unlabelled steroid to Rhesus monkey, serum samples were collected at various periods, and radioactivity was counted with or without reverse-phase HPLC separation in advance. Pharmacokinetics of NETO and NETO-AC were compared with those of norethisterone (NET) and norethisterone acetate (NET-AC) respectively which were studied in a similar experimental design. The results indicated that the serum concentration-time curve of NETO and NET could be adequately described by a two-compartment model. Average t 1/2 ka, t 1/2 alpha and t 1/2 beta with standard deviation for oral administration were 0.21 +/- 0.08 (h), 1.28 +/- 0.31 (h) and 10.01 +/- 4.59 (h) for NET and 0.37 +/- 0.81 (h), 0.90 +/- 0.26 (h) and 8.55 +/- 2.21 (h) for NETO respectively. NETO metabolized to NET which had a similar serum profile with its precursor. NET-AC also metabolized to NET, but more rapidly. It disappeared from blood 8-12 h after nasal feeding. NETO-AC was non-detectable at all when given orally because it metabolized immediately and extensively in the animal body. Its major metabolites, NETO, NET and NET-AC already appeared in the first blood sample drawn 15 min after administration. NETO-AC, when injected intravenously, declined abruptly and could not be detected 4 h later. Among the metabolites, only the deacetylated products (NET and NETO) reached relatively higher levels and sustained longer in blood.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacokinetics of norethindrone-3-oxime and norethindrone in rhesus monkeys].

After intravenous administration or nasal feeding of (6, 7-3H)-labelled norethindrone-3-oxime (NETO) or norethindrone (NET) to rhesus monkeys, the serum concentrations were determined by measuring the radioactivity after separation with HPLC. The serum concentrations of total extractable radioactivity were also measured without HPLC separation. In cases of nasal feeding, NETO and NET were quickly absorbed, and almost all of them were eliminated within 24 hours. NETO, when given via both routes, was partly metabolized to NET and partly remained in original form. The blood concentration--time curves for NETO and NET were adequately fitted to two compartment models. No significant difference in pharmacokinetic parameters between the two drugs was observed. The absolute bioavailability for NETO and NET were found to be 64.46 +/- 34.60% and 35.02 +/- 26.49% respectively.

Follow-up studies on Epstein-Barr virus IgA/VCA antibody-positive persons in Zangwu County, China.

Serological mass surveys were carried out in Zangwu County, China, using an immunoenzymatic test. 3,533 persons were found to have Epstein-Barr virus (EBV) IgA/VCA antibody among 148,029 persons age 30 years and older who were tested during 1978-1980. Among the IgA/VCA antibody-positive persons, 55 nasopharyngeal carcinoma (NPC) cases were detected. Follow-up studies were carried out yearly on the IgA/VCA antibody-positive persons for 1-3 years, and 32 additional NPC patients were diagnosed. IgA/VCA antibody was detected 8-30 months (average, 13 months) prior to the clinical diagnosis of stage I NPC. There was no marked difference in geometric mean titers of IgA/VCA antibody between the period before onset of NPC and after diagnosis at stage I, but antibody titers were higher during stages II-IV. The NPC detection rates for all persons tested serologically and for IgA/VCA antibody-positive persons, respectively, was 2- and 82-fold the annual incidence of NPC in the general population of the same age group. These data further indicate that serological testing is valuable for the diagnosis of NPC, especially in its early stages, and that EBV may play an important role in the development of NPC.