Prenatal diagnosis in Treacher Collins syndrome using combined linkage analysis and ultrasound imaging.

Treacher Collins syndrome is an autosomal dominant disorder of facial development, the features of which include conductive hearing loss and cleft palate. In the current investigation, linkage analysis has been used to make first trimester diagnostic predictions in a pregnancy at high risk of producing an affected child. The results of this analysis predicted that the child would be affected. As predictions of the severity of the disease were not possible, the pregnancy was also assessed by ultrasound imaging. This confirmed the affected diagnosis and predicted that the child would be severely affected.

Placental biopsy in the third trimester of pregnancy.

Forty-two women with abnormal ultrasound findings after 27 weeks' gestation underwent a placental biopsy. In 39 cases, a karyotype was obtained from a direct preparation within 48 h, five abnormal karyotypes being detected (four trisomies and a triploidy). One confirmed placental mosaic was also detected. In one case, a small terminal deletion of chromosome 7 was not detected at the time due to the quality of the preparation. A karyotype can be obtained from a direct preparation in the third trimester in over 90 per cent of cases, the quality of the preparation allowing the reliable detection of abnormalities of chromosome number. We believe that this technique may be usefully, reliably, and safely employed in the third trimester of pregnancy by those with an interest in antenatal ultrasound diagnosis who do not have immediate access to a cytogenetics laboratory and who feel that cordocentesis is inappropriate for their situation.

Prenatal diagnosis of severe osteogenesis imperfecta.

The ultrasound findings in a series of 15 prenatally diagnosed cases of severe osteogenesis imperfecta types IIA, IIB, IIC, and III are described, eleven being detected on routine scans of women with no relevant history. As most cases of osteogenesis imperfecta type IIA are dominant sporadic mutations, the importance of prenatal diagnosis during routine scanning at a local level is emphasized. In addition to characteristic broad, shortened and fractured long bones, striking features of the chest and head are highlighted which may be encountered during a routine scan, prompting further assessment.

Carcinogen-induced nuclear enlargement in cultures of rat tracheal primary epithelial cells.

Rat tracheal epithelial cells were cultured for 72 hr and then exposed for 3 hr to a range of test chemicals, including non-carcinogens, and direct-acting and activation-dependent carcinogens. The cells were then washed and cultured in fresh medium without the test chemicals for a further 24, 72 or 120 hr. Nuclear size measurements were then made. At 72 and 120 hr after exposure, those cultures treated with the non-carcinogens pyrene and anthracene had distributions of nuclear area similar to those of the solvent controls. All cultures treated with activation dependent carcinogens (N-nitrosopyrrolidine, N-nitrosodimethylamine, benzo[a]pyrene, dimethylbenz[a]anthracene or 4-nitroquinoline-N-oxide) or direct-acting carcinogens (nitrogen mustard or methylmethanesulphonate) showed a shift in distributions to the right, indicating enlarged nuclei. These results indicate that carcinogen-induced nuclear enlargement can occur in cultures of rat primary tracheal epithelial cells, and that this may be a useful indicator system for respiratory carcinogens.

The short-term effects of carcinogens and sulphur dioxide on the nuclear size of rat nasal epithelial cells.

Enlarged nuclei have been observed frequently as an early carcinogen-induced change in both cultured cells and in target tissues in vivo. The purpose of this work was to examine the occurrence of nuclear enlargement in the upper respiratory tract of rats to provide further evidence of whether nuclear enlargement is a reliable marker of carcinogenesis, and if it could be used as a short-term test for respiratory carcinogens. Carcinogen-induced nuclear enlargement is best demonstrated in vivo when the tissue involved has been undergoing rapid replication. Male Wistar albino rats were simultaneously exposed to an atmosphere containing sulphur dioxide (which caused a hyperplastic response in the nasal cavity) and received an i.p. injection of a nitrosamine. Sections were prepared from the nasal cavity, and the nuclear areas of respiratory epithelial cells were measured. There were some increases in nuclear size 24 and 72 h after the start of treatment. The reversal of this effect 120 h after the start of treatment may have been due to the loss of the normal ciliated mucosal epithelium, and subsequent loss of metabolic capability.

Renal and hepatic lesions induced by 2,2,4-trimethylpentane.

The renal changes produced by 2,2,4-trimethylpentane, a constituent of unleaded gasoline, are studied in Wistar rats. The compound was given at a dose of 2 ml/kg daily by gavage dissolved in corn oil (2:1) to nine Wistar Albino rats. Nine control male rats received an equivalent dose of corn oil. Six animals were housed in metabowls to allow the collection of urine for enzyme and urinanalysis. The remaining three animals of each group were housed in a normal animal cage. After 2 days of treatment, all the test rats were noted to have lost weight and were killed on this or on the subsequent day. Macroscopic examination of the livers and kidneys revealed no visible lesions on the kidney, but two of the rats had white, slightly raised patches on the liver. Microscopic examination demonstrated centrilobular and confluent necrosis, hydropic degeneration and vacuolation of hepatocytes. Microscopic examination of the kidneys indicated eosinophilic hyaline droplet accumulation in the cells of the tubules, and tubular dilation. Analysis of plasma alkaline phosphatase and aspartate transaminase activity revealed increases consistent with liver damage. Analysis of urinary N-acetyl-beta-glucosaminidase and alkaline phosphatase activity showed increases consistent with renal toxicity. An apparent increase in the amount of cellular debris in the urine was also found, when the sediment was examined microscopically. From this study, it would appear that 2,2,4-trimethylpentane possess hepatotoxic as well as nephrotoxic properties.

Clinical and urodynamic assessment of the porcine dermis bladder sling in the treatment of genuine stress incontinence.

Fifty women, aged between 37 and 76 years, underwent a bladder sling operation for urinary incontinence using porcine dermis. All patients had undergone previous unsuccessful vaginal surgery for genuine stress incontinence and had stable bladders. Thirty-nine patients (78%) were made continent of urine, both subjectively and on urodynamic testing.