Comparison of efficacy and safety of empagliflozin vs linagliptin added to premixed insulin in patients with uncontrolled type 2 diabetes: A randomized, open-label study.

AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase (DPP)-4 inhibitors added to insulin regimens in patients with type 2 diabetes mellitus (T2DM) can improve glycaemic control. This study compared the efficacy and safety of empagliflozin and linagliptin added to premixed insulin therapy in patients with poorly controlled T2DM. METHODS: In this 24-week, open-label, parallel-design randomized controlled trial, patients with poorly controlled T2DM despite a premixed insulin regimen were randomized to receive 5mg of linagliptin (n=53) or 25mg of empagliflozin (n=53) for 24 weeks. RESULTS: At week 24, changes in glycated haemoglobin (HbA1c) from baseline were -0.06±0.17% and -1.01±0.16% in the linagliptin and empagliflozin groups, respectively, and the mean treatment HbA1c difference was -0.88% (95% CI: -1.33, -0.43). At week 24, the empagliflozin group showed significant reductions, compared with the linagliptin group, in fasting plasma glucose (P<0.001), body weight (P<0.001), systolic blood pressure (P=0.003) and total daily insulin dose (P=0.042). Hypoglycaemia was reported to be slightly, and not significantly, higher in the empagliflozin group vs linagliptin group (30.2% vs 22.6%, respectively; P=0.51). Similar percentages of patients (1.9%) had urinary tract infections in the two groups. CONCLUSION: In Asian patients with inadequately controlled T2DM while taking premixed insulin, the addition of empagliflozin for 24 weeks provided better glycaemic control and greater reductions in body weight and systolic blood pressure than the addition of linagliptin. Clinical Trial Registration #: NCT03458715.

Characterization of Philadelphia-chromosome-positive acute leukemia by clinical, immunocytochemical, and gene analysis.

Philadelphia chromosome (Ph') was detected at presentation in 10 out of 110 patients with acute lymphoblastic leukemia (ALL) and five of 168 patients with acute myelogenous leukemia (AML). Two other ALL patients who had studies at relapse were also included in the analyses. One of the 12 Ph'-positive (Ph+) ALL patients had simultaneous expression of myeloid-associated antigen on the leukemic blasts, while all the five AML patients coexpressed markers of lymphoid cells. Double labeling of the cells with myeloperoxidase and CD10 on three Ph+ AML cases showed that most leukemic blasts expressed either myeloperoxidase activity or CD10 but not both. Cross-lineage gene rearrangements of T-cell receptor (TCR) beta-chain gene were detected in three of the eight Ph+ ALL patients tested. All the four Ph+ AML cases studied showed immunoglobulin heavy chain gene rearrangements, and three of them also had simultaneous rearrangements of TCR beta-chain gene. The results revealed that Ph+ acute leukemia in this study belonged either to ALL or mixed lineage leukemia, and none was pure AML. This finding is contrary to that of acute blast crisis of chronic myelogenous leukemia in which the majority of patients had myeloid transformation. Rearrangements of bcr were detected in four of the 10 Ph+ ALL and three of the four Ph+ AML patients tested. No significant difference was noted in the clinical or hematologic manifestations among Ph+ leukemia with or without bcr rearrangements.

Cloning and expression in Escherichia coli of the gene encoding an extracellular deoxyribonuclease (DNase) from Aeromonas hydrophila.

The gene encoding an extracellular DNase from Aeromonas hydrophila CHC-1 has been cloned and sequenced. Following expression of the dns in Escherichia coli, it was revealed that some of the cloned enzyme was present in the cell-free extracellular supernatant fluid, and there was no cell lysis and concurrent release of cytoplasmic or periplasmic proteins. Therefore, results suggest that E. coli cells were capable of secreting the DNase extracellularly, albeit very inefficiently. The dns is transcribed from its own promoter in E. coli, and expressed as a 25-kDa product, as determined by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis of the culture supernatant preparations followed by a DNA-hydrolysis assay. Nucleotide sequence analysis predicted a single open reading frame of 690 bp encoding a 230-amino acid (aa) polypeptide, with a potential 20-aa signal peptide located at the N terminus of the predicted protein. The deduced aa sequence of the entire protein is highly homologous with that of the DNase of Vibrio cholerae.

Acute leukemic transformation of myelodysplastic syndrome--immunophenotypic, genotypic, and cytogenetic studies.

The clinical and biological characteristics of myelodysplastic syndrome (MDS) in acute leukemic transformation were studied in 23 patients. All had myeloid transformation according to FAB criteria, but coexpression of lymphoid-associated antigens was detected in five of the 20 patients who underwent an immunophenotypic study. Rearrangement of the immunoglobulin heavy chain gene was also observed in one of the five patients who coexpressed lymphoid markers and that of the T-cell receptor beta chain gene in another one. None had pure lymphoid transformation. Clonal chromosomal abnormalities were noted in 12 (63%) of the 19 patients who underwent cytogenetic study, most commonly - 7 (six patients or 32%). In the 18 patients who underwent serial analyses both at MDS diagnosis and at acute transformation, seven (39%) underwent karyotypic evolution. The most common new or additional aberrations were +8 and +21. N-ras gene mutation was detected in two of the nine patients at acute leukemic transformation. The median interval from diagnosis of MDS to onset of acute transformation was 10 months (1-36 months). Patients with a normal karyotype at diagnosis had a significantly longer chronic phase duration than those with chromosomal abnormalities (median of 20 months vs. 5 months). However, all had a short survival time after diagnosis of acute leukemia, whether chromosomal anomalies were present or not.

Cytogenetic characterization of a nasopharyngeal carcinoma cell line and its subline.

Cytogenetic results of a nasopharyngeal carcinoma (NPC) cell line NPC-TW039 and its subline NPC-TW039-N1, established from the nude mouse transplant, were reported. This is the third case of NPC presented with banded karyotype, to date, in the literature. A 3q + marker chromosome, with involvement of band q25 similar to that present in the two previously reported cases, was detected in most tumor cells from both cell lines. The structural chromosome abnormalities of NPC-TW039-N1 were similar to its original cell line, NPC-TW039, except that the subline lost one marker chromosome and gained a new one.

Cytogenetic evidence of multifocal origin of a unilateral retinoblastoma. A help in genetic counseling.

Retinoblastoma (Rb) occurs in two different genetic forms, hereditary and nonhereditary. Patients with nonhereditary Rb have unilateral, unifocal tumors, and those with the hereditary form usually have bilateral, multiple tumors. However, about 15% of patients with unilateral disease actually have multifocal tumors due to the hereditary form of Rb. Distinction between unilateral hereditary and sporadic Rb is very important both to the patient, who is at risk of later development of other malignancies, and to any future siblings and offspring. With only clinical data, the discrimination may be difficult. The cytogenetic detection of multiple unrelated clones in the tumor is very helpful for differential diagnosis because this finding strongly suggests the presence of a prezygotic germ cell mutation, which is heritable. A 23-month-old Chinese boy was found to have a single retinoblastoma at the right eye. Cytogenetic study of the tumor cells revealed three abnormal clones. Two of them were related, but the third one had completely different markers, suggesting a hereditary, multifocal origin of the tumor. None of the three clones showed an abnormality of 13q, which is present in about 21% of all Rb patients.

Cytogenetic characterization of Epstein-Barr virus-associated T-cell malignancies.

Recently, Epstein-Barr virus (EBV) infection has been found not only to be associated with Burkitt lymphoma and nasopharyngeal carcinoma but also with some T-cell malignancies. Cytogenetic studies were performed on four Chinese patients with EBV-associated T-cell neoplasms: three peripheral T-cell lymphomas and one large granular lymphocyte leukemia with coexpression of T-cell antigen. Clonal chromosomal abnormalities were detected in all four patients. Rearrangements of chromosome 7 were observed in three patients: one at 7p22, one at 7q35 or 36, and the remaining one at both sites. The last patient also had a chromosomal abnormality involving 14q11. Trisomy of part of the 1q segment was detected in two patients. The results revealed that the chromosomal abnormalities in these patients were similar to those observed in other T-cell lymphomas. Further studies on more patients are necessary to find out whether there are specific chromosomal aberrations in EBV-associated T-cell neoplasms.

Chromosomal characteristics of Ph-positive chronic myelogenous leukemia in transformation. A study of 23 Chinese patients in Taiwan.

Cytogenetic study was performed in the past 3 years on 23 Chinese patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) in transformation; seven were in accelerated phase and 16 in acute blast crisis. Chromosomal abnormalities in addition to Ph were found in three (43%) of the patients at accelerated phase and 14 (88%) of the patients at blast crisis. The common nonrandom chromosomal aberrations were double Ph, trisomy 8, trisomy 19, and trisomy 21, which occurred in 47%, 41%, 35%, and 29%, respectively, of the total patients with extra chromosomal abnormalities. Isochromosome for the long arm of chromosome 17 was found in only one patient. In patients with blast crisis, the type of blast cell was characterized through morphologic, cytochemical, and immunocytochemical studies. Eleven cases were classified as myeloid and five as lymphoid transformation. Trisomy 8, 19, and 21 were detected only in patients with myeloid blast crisis. This study also revealed a high incidence of trisomy 21 and a low incidence of i(17q) in Chinese patients with transformation of CML.

Chromosome studies on 30 Chinese patients with acute nonlymphocytic leukemia in Taiwan.

Cytogenetic studies were performed on 32 consecutive Chinese patients with de novo acute nonlymphocytic leukemia (ANLL) in Taiwan. Of the 30 patients with adequate specimens, 20(66%) had clonal chromosome abnormalities. Structural rearrangements were detected in 18 of them. Seven (four were children) of the 16 patients with M2 ANLL had t(8;21). All six patients with acute promyelocytic leukemia (APL; M3 subtype) had t(15;17). Two patients with M4 type leukemia and abnormal bone marrow eosinophils had inv(16)(p13q22). Another M4 patient with a mild increase of morphologically normal eosinophils in the bone marrow had an abnormal chromosome #16, t(1;16)(q21;p13) in which 16q22 was not involved. One patient with M5 ANLL had t(9;11). Only two patients had a numerical change as the sole abnormality. None of the patients had loss or deletion of chromosome #5 or loss of chromosome #7, and only one had a deletion of 7q. This study revealed a high incidence of t(8;21), t(15;17), and a low incidence of -5/5q- or -7/7q- in Chinese patients with ANLL.

Comparison of clinical and biologic features between myeloid and lymphoid transformation of Philadelphia chromosome positive chronic myeloid leukemia.

Analysis of clinical and biologic features of chronic myeloid leukemia (CML) in blast crisis (BC) was performed on 36 patients: 25 had myeloid and 11 had lymphoid transformation. The median duration from diagnosis to onset of BC was significantly shorter in patients with lymphoid BC (6 months) than in those with myeloid BC (41 months). Patients in lymphoid transformation showed better response to therapy and had a significantly longer median survival time after BC than patients with myeloid transformation (56% vs 0% and 10 months vs 4 months, respectively). The leukemic cells from all the patients with lymphoid BC showed B-cell immunophenotype, confirmed by the presence of immunoglobulin (Ig) heavy chain gene rearrangements in the five patients studied. Two of the eight patients with complete marker study expressed myeloid-associated antigens on the blasts. A high incidence of CD7 expression (7/17 or 41%) was found in patients with myeloid BC, but none of the patients who had DNA analysis showed rearrangement of T-cell receptor beta chain gene. Chromosomal abnormalities +8, +19, +21, and i(17q) were detected only in the patients with myeloid BC but not in those with lymphoid BC. Combined analysis of the patients in this series and those reported previously has revealed a statistically significant difference in the distribution of bcr breakpoints between myeloid and lymphoid BC: the bcr breakpoints in more than half of the patients with myeloid crisis were mapped to Zone 2 while those in patients with lymphoid crisis occurred most frequently in Zone 3.

Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan.

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.

Cytogenetic studies, ras mutation, and clinical characteristics in primary myelodysplastic syndrome. A study on 68 Chinese patients in Taiwan.

Cytogenetics and clinical features were studied for 68 Chinese patients with primary myelodysplastic syndrome (MDS). Ras mutation was analyzed in 25 of them. Thirty-four patients (50%) had clonal chromosomal abnormalities at initial analysis. The most common cytogenetic aberrations were -7, +8, 5q-, and 20q-, which occurred in 11 (16.2%), seven (10.3%), five (7.4%) and three patients, respectively. The incidence of -7 was higher and that of 5q- lower in our patients than in patients from most other geographic areas. The 17 patients with multiple chromosomal abnormalities had a significantly shorter median survival (9 months) than the 34 patients with normal karyotype (33 months) and the 17 patients with patients with single anomalies (26 months). Evolution to acute leukemia occurred in 20 patients (29%) after a median interval of 8 months following the diagnosis. Patients with multiple cytogenetic changes at initial analysis or in subsequent studies had a significantly higher frequency of acute transformation than others (55% vs. 18.6%, p = 0.007); the same was not true if only the data of initial study were considered. Serial cytogenetic studies are important in patient follow-up. N-ras mutation was detected in 5 (20%) of 25 patients within the study. There was no correlation between the gene mutation and acute transformation. But combing the data of N-ras mutation and cytogenetics, patients with either the N-ras mutation or clonal chromosomal abnormalities were at significantly higher risk for developing acute leukemia than those with neither of the changes (77% vs. 25%).

Cytogenetic study of acute lymphoblastic leukemia and its correlation with immunophenotype and genotype.

Among 72 Chinese patients with acute lymphoblastic leukemia (ALL), 50 had clonal chromosomal abnormalities. Structural abnormalities were detected in 42 patients: these included t(9;22) in 9, t(1;19) in 6, t(4;11) in 5, del(11)(q23) in 4, and del(6q) in 4. Adults had a higher incidence of t(9;22) and t(1;19) but a lower incidence of t(4;11) and hyperdiploid greater than 50 karyotype than children. A significant difference was also noted in white blood cell (WBC) count among various karyotypic groups. Patients with chromosomal abnormalities t(9;22), t(1;19), t(4;11) and del(11) (q23) had a shorter complete remission duration as compared with patients free of these abnormalities. Immunophenotyping was performed on 69 patients. All patients with t(9;22), t(1;19), and t(4;11) had B-lineage ALL restricted to certain stages of maturation: groups III and IV, groups IV and V, and group II, respectively (according to the classification of Foon and Tood). Among patients with t(9;22), t(4;11), and del(11)(q23), which have been considered to be associated with acute mixed-lineage leukemia, one each, respectively, showed myeloid antigen expression on the leukemic blasts (My+ ALL). No cross-lineage rearrangements of immunoglobulin (Ig) or T-cell receptor (TCR) genes were detected in these karyotypic subgroups of patients who underwent gene analysis.

Norplant subdermal contraceptive system: experience in Taiwan.

From November 1988 to December 1994, a total of 567 female volunteers were enrolled in Norplant implant studies at the National Taiwan University Hospital. After a median follow-up of 29 months, only 3 of the 529 available cases became pregnant (a cumulative rate of 1.2 pregnancies per 100 users over 5 years). Chromosome analysis of 2 of the 3 abortuses revealed 46,XX/46,XX,inv(3) and 46,XX. Menstrual problems were the most common adverse effects and were also the main reason for discontinuation (65%, 108/166). The continuation rate was 90%, 78%, 70%, 61%, and 42% at the end of 1, 2, 3, 4, and 5 years after insertion, respectively. In the 21 patients who wished to become pregnant, fertility recurred soon after removal of the Norplant implants. The data suggested that the Norplant implants system is a highly effective, safe, and long-acting method of reversible contraception. It would be worthwhile to introduce this contraceptive system to Taiwan's family planning program.

PIP: Between November 1988 and December 1994 health providers at the National Taiwan University Hospital enrolled 567 women aged 17-47 in the Norplant implant studies that aimed to evaluate the benefits and side effects of Norplant as another contraceptive method choice. They followed the women for a median of 29 months. 38 cases were lost to follow-up. The 5-year contraceptive effectiveness rate was 98.8%. The 3 pregnancies (2 intrauterine and 1 ectopic) occurred during the 24th, 45th, and 47th months of use. None of the women who became pregnant weighed more than 70 kg. Two of the aborted fetuses had chromosomal abnormalities (46,XX/46,XX,inv(3) and 46,XX). 29.9% of the Norplant users had menstrual problems. Even though irregular bleeding occurred to 19.7% of Norplant users, hemoglobin levels increased after Norplant use (p 0.05). Triglycerides and total cholesterol levels decreased (p 0.05). None of the women developed thromboembolism. The Norplant continuation rate was 89.7% at 1 year, 78% at 2 years, 70% at 3 years, 61% at 4 years, and 42.4% at 5 years. The leading reason for implant removal was menstrual problems (108). The implants were removed during one sitting without x-ray or ultrasound identification in all 166 women who stopped using Norplant before 5 years and the 16 women who stopped using it at the end of 5 years. 78% of women who discontinued Norplant to become pregnant were pregnant within one year following removal. All their infants were normal. These findings suggest that Norplant is a safe, effective, and acceptable contraceptive method and that the family planning program should introduce Norplant to its contraceptive mix.

An immunohistochemical study of E-cadherin expression with correlations to clinicopathological features in gastric cancer.

BACKGROUND/AIMS: Reduced expression of E-cadherin leading to loss of cellular adhesion is crucial for cancer invasion and metastasis. The aim of this study is to investigate the role of E-cadherin in gastric tumorigenesis. METHODOLOGY: Immunohistochemical expression of E-cadherin was analyzed and correlated with clinicopathological characteristics of 122 patients with gastric cancer. RESULTS: Reduced E-cadherin expression was noted in 71 tumors (58.2%), while all normal epithelium showed a normal expression. Correlation of E-cadherin status to histological subtypes and growth patterns revealed a significantly higher frequency of reduced expression in diffuse type (46/60, 76.7%), advanced tumors (48/68, 70.6%) and stage III/IV (39/53, 73.6%) than that in intestinal type (25/62, 40.3%, p<0.0001), early tumors (23/54, 42.6%, p<0.005) and stage I/II (32/69, 46.4%, p<0.005) respectively. Moreover, abnormal expression was more frequent in tumors with positive lymph node metastasis (45/62, 72.6%), peritoneum seeding (10/11, 90.9%) and venous permeation (27/37, 73%) than that in tumors without lymph node metastasis (26/60, 43.3%, p<0.005), peritoneum seeding (61/111, 55.0%, p<0.05) and venous permeation (44/85, 51.8%, p<0.05). There is no statistical difference between E-cadherin expression and the status of perineural invasion or H. pylori infection. Analysis of survival for patients demonstrated that reduced E-cadherin expression was correlated with poor prognosis. CONCLUSIONS: These data indicate that impaired expression of E-cadherin is an important characteristic of gastric cancer and contributes to histogenesis, tumor growth, metastasis and poor survival.

Relationship of p53 and c-erbB-2 expression to histopathological features, Helicobacter pylori infection and prognosis in gastric cancer.

BACKGROUND/AIMS: Conflicting results concerning the relationships between abnormal expression of p53 and c-erbB-2 and biologic behavior of gastric cancer are noted. Therefore, overexpression of p53 and c-erbB-2 in relation to the following aspects of gastric cancer: tumor histopathology, Helicobacter pylori infection, and prognosis are explored. MATERIALS AND METHODS: Expression of p53 and c-erbB-2 by immunohistochemistry was correlated with histopathology, H. pylori infection and prognosis of gastric cancer in 112 patients. RESULTS: Positive p53 staining was found in 61 (54.5%) of 112 tumors examined. There was no association of p53 expression with sex, age, lymph node metastasis, H. pylori infection or prognosis. A significantly higher frequency of p53-positive staining was observed in advanced (60.7%), intestinal (69.8%) and cardia (76.5%) than in early (30.4%, p < 0.01), diffuse (34.7%, p < 0.01) and noncardia (50.5%, p < 0.05) carcinoma, respectively. Expression of c-erbB-2 was found in 34 cases (30.3%), and was not related to sex, age, H. pylori infection and tumor location. Tumors with positive c-erbB-2 staining appeared to behave more aggressively in view of higher rates of nodal metastasis (38.0% vs 17.1%, p < 0.05), advanced stage (37.1% vs 4.3%, p < 0.01) and poor mean survival (p < 0.01). Patients with intestinal type tumors also had a significantly higher rate of c-erbB-2 expression than those with diffuse tumors (39.7% vs 18.4%, p < 0.01). CONCLUSIONS: Our results indicate that immunohistochemical expressions of p53 and c-erbB-2 are significantly associated with some histopathological phenotypes. Genetic alterations of c-erbB-2 or p53 may not be affected by H. pylori infection. C-erbB-2 expression may be used as a marker for identifying more aggressive gastric cancer for designing further therapy.

Complete androgen insensitivity syndrome. Molecular characterization in two Chinese women.

OBJECTIVE: To study the molecular basis of complete androgen insensitivity syndrome (AIS). STUDY DESIGN: The coding region of the human androgen receptor (hAR) gene in two women with AIS was amplified with polymerase chain reaction using 12 pairs of oligonucleotide primers and then sequenced with a dye terminator method. RESULTS: Both patients had mutation in exon E of the androgen-binding domain. In one patient, codon 732 GAC (aspartic acid) was changed to ACC (asparagine), and her CAG polyglutamine tract had 27 repeats. In the other patient, codon 765 GCC (alanine) was changed to ACC (threonine), and her CAG polyglutamine tract in exon A had 19 repeats. CONCLUSION: Except for CAG polyglutamine polymorphism, these two missense mutations were the only differences detected in the coding region of the hAR gene. Both mutations involved the CpG sequence, which has been regarded as a mutation hotspot. To the best of our knowledge, these two mutations have not been observed before in Chinese women. Elucidation of the molecular defects of AIS patients would be very helpful for genetic counseling and prenatal diagnosis.

Congenital adrenal hyperplasia. Molecular characterization.

OBJECTIVE: To study the molecular defects of congenital adrenal hyperplasia (CAH). STUDY DESIGN: Twenty Chinese patients, including 8 with salt-wasting (SW) type CAH, 11 with simple virilizing (SV) type CAH and 1 with nonclassical (NC) type CAH, were recruited. Two rounds of the polymerase chain reaction (PCR) were used to study the 21-hydroxylase gene (CYP21). The primary PCR amplified CYP21-specific DNA fragments, and the secondary PCR used products from the primary PCR for analysis of amplification-created restriction sites (ACRS) and direct DNA sequencing. In all patients, ACRS analysis was done at 12 possible mutation sites, and then direct DNA sequencing was performed to confirm or define the molecular defects. RESULTS: Ten different mutations, including nine point mutations and gross gene deletion or conversion, were found in this study. Of the nine point mutations, eight could be easily detected by ACRS analysis. The three most common mutations were codon (CD)172 t-->a (I172N), IVS-II 656 c/a-->g, and gross gene deletion or conversion, accounting for 27.5% (11/40 alleles), 25% (10/40) and 20% (8/40) of all identified mutations, respectively. All SW patients were compound heterozygotes of IVS-II 656, gross gene deletion or conversion, or other severe defects, including CDs236 (t-->a) (I236N)+ 237 (t-->a) (V237E)+ 239 (t-->a) (M239K), CD306 (+t), CD318 (c-->t) (Q318X) and CD356 (c-->t) (R356W) mutations. All SV patients had one allele with a CD172 (I172N) mutation. One allele of an NC patient had a CD183 (c-->g) (D183E) mutation, and the other allele was not defined. In the whole series, four alleles (10%) had more than one mutation. CONCLUSION: We found 10 different mutations in this study. The correlation between genotypes and phenotypes was compatible with the reported data. Two rounds of PCR and ACRS analysis may provide important information for genetic counseling, prenatal diagnosis and management of families at risk for CAH.

Rapid prenatal determination of fetal sex by polymerase chain reaction on amniocyte DNA.

Sex determination in early gestation is important for fetuses at risk for X-linked disorders or congenital adrenal hyperplasia. One hundred and seventy consecutive samples of amniocytes were collected between the 12th and 31st gestational week. Seven women received early amniocentesis before the 14th week. Fetal sex was determined by amplification of Y-specific DNA fragments within five hours. All results of the polymerase chain reaction, except for one false-negative, were compatible with cytogenetic analyses. Polymerase chain reaction of amniocyte DNA provides a rapid technique for sex determination in early gestation with high specificity and sensitivity.

Neurenteric cyst at craniocervical junction: report of a case.

The authors report a rare case of neurenteric cyst at the foramen magnum presenting with a central cord syndrome and dysfunction of the lower cranial nerves. A magnetic resonance imaging study showed a cystic lesion over the lower medulla oblongata and C1-2 spinal cord. Differentiation between a neurenteric cyst and an epidermoid cyst was difficult. Successful total removal of the cyst was performed. The lesion consisted of an enteric cyst lined with a mucus-secreting columnar epithelium, containing highly proteinaceous supernatant and thick mucus deposit. The patient recovered dramatically after surgery.