Direct chromosome analysis from neonatal cord blood.

Direct chromosome preparations of neonatal cord blood provides the unique opportunity for rapid chromosome analysis (turnaround time; 6 hr), without the necessity of bone marrow aspiration. Based on 42 samples we confirm the finding of Garnham and Sutherland [1987] for suitability of cord blood for direct chromosome preparation. Procedural modifications are provided for higher yield of cells for chromosome analysis. The procedure may well be of major significance for rapid diagnosis of neonates who suffer from aneusomy.

"De novo" duplication Xq23-->Xq26 of paternal origin in a girl with a mildly affected phenotype.

We report a de novo dup(X)(q23-->q26) in a 3-year-old girl with growth retardation, developmental delay, and minor anomalies. X-inactivation in lymphocytes by BRDU labeling showed the abnormal X was late replicating. The androgen receptor assay (HAR) demonstrated a skewed methylation (88.8%) of the paternal allele and a 11.2% methylation of the maternal allele. These data, which suggest the duplication was paternally inherited, are the first parental-origin identification of a duplication Xq. The mild phenotype of the patient may be related to the size and region of the duplication, the low percentage of a dup(X) active detected by the HAR assay, or a combination of these mechanisms.

Clasped-thumb mental retardation (MASA) syndrome: confirmation of linkage to Xq28.

We describe a 5-generation Hispanic family with 13 males and 1 female affected with MASA syndrome. The proposita, a 17-year-old female, and her affected male relatives shared many of the cognate manifestations--mental retardation (14/14), aphasia or delayed speech (13/13), shuffling gait (8/13), adduction of thumbs (14/14)--as well as scoliosis (2/13) and increased deep tendon reflexes in the lower extremities (10/13). Southern analysis with the polymorphic DNA probes DXS14 (Xp11), DXS72 (Xq21), and F8C (Xq28) confirmed linkage to the Xq28 region with a maximum lod score of 3.01 for this family.

The tricho-rhino-phalangeal syndrome with exostoses (or Langer-Giedion syndrome): four additional patients without mental retardation and review of the literature.

We report on four patients with tricho-rhino-phalangeal syndrome with exostoses (TRPSE) who were not mentally retarded and review 32 previously published cases. These data enable more complete delineation of the phenotype and document the variability of the clinical and radiographic manifestations. Information on the genetics and the association with del(8q) is discussed, as are management and avenues for further investigation. The apparent variability of intelligence in TRPSE patients together with the high incidence of other problems, including significant delay in speech development and hearing loss, make systematic multidisciplinary evaluation and long-term treatment necessary to achieve the best outcome.

Interstitial deletions 4q21.1q25 and 4q25q27: phenotypic variability and relation to Rieger anomaly.

We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months of hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region.

De novo partial duplications 1p: report of two new cases and review.

We describe two de novo intrachromosomal duplications of 1p. One case is a dir ins dup(1)(q21p21p31) in a newborn girl with low birth weight, growth retardation, and tetralogy of Fallot. The other is a 10-month-old girl with developmental delay, craniosynostosis, plagiocephaly, and an inv dup 1p34.1p31. Although, these patients have manifestations in common with previous cases, they do not establish a syndrome. Interestingly, all males with duplications spanning 1p31 had genital anomalies, whereas females with duplications of the same region had normal genitalia. Thus, genes within 1p31 appear to control the development of male genitalia and tentatively exclude effects of tda1, a sex-determining gene in a region of mouse chromosome 4 syntenic to 1p36 in man. However, it is necessary to identify the human tda1 homologue and candidate genes within 1p31 before drawing final conclusions.

Intestinal metaplasia in endoscopic biopsy specimens of gastric mucosa.

A total of 1412 consecutive cases of endoscopic gastric biopsy, carried out over a four year period, were reviewed and specimens were examined histochemically to determine the prevalence of intestinal metaplasia and its variants. Three types were characterised: complete intestinal metaplasia and two classes of incomplete intestinal metaplasia (type IIa and type IIb) depending on the absence or presence, respectively, of sulphomucins within mucin secreting columnar cells. Type IIb intestinal metaplasia was significantly more common in patients with gastric carcinoma (p less than 0.001) and in those with dysplasia (p less than 0.001) than in patients with benign gastric pathology. No such association was found with either type I or type IIa intestinal metaplasia. In addition to those present in the columnar cells of type IIb intestinal metaplasia, sulphomucins were also commonly found in goblet cells of all three types of metaplasia. The presence of sulphomucins in goblet cells, however, was not significantly associated with gastric carcinoma or dysplasia. The significance of the different types of intestinal metaplasia in relation to the pathological findings is discussed.

Spectrum of renal tubular damage in renal failure secondary to cirrhosis and fulminant hepatic failure.

Measurements of urinary lysozyme were used to evaluate renal tubular integrity in 34 patients with cirrhosis or fulminant hepatic failure who had developed renal impairment. In 18 of the patients the lysozyme values were normal but in the remaining 16 were increased, supporting previous concepts that renal failure complicating hepatocellular disease may occur both without and with tubular necrosis. The lysozyme values were inversely related to the creatinine clearance, suggesting that the development of tubular necrosis may be determined by the level of renal perfusion. The validity of simpler laboratory tests often used to assess renal tubular integrity--namely, the urine sodium concentration, the urine:plasma osmolality ratio, and casts in the urine sediment--was evaluated by comparison with the lysozyme measurements. The urine sodium concentration was of most value and the findings in the sediment were of no value at all.

Faecal steroids and colorectal cancer: steroid profiles in subjects with adenomatous polyps of the large bowel.

In this necroscopy study the relation between carriage and size of colorectal polyps was correlated with luminal steroid concentrations in respect to malignant risk. Of the 92 subjects entered into the study, 68 had adenomatous polyps of the large bowel, of which 19 had adenomas > 0.9 cm in diameter (large adenomas), 26 in the range 0.5-0.9 cm in diameter (medium adenomas) and 23 of 0.4 cm or less in diameter (small adenomas). Sixty-three percent of subjects carrying large adenomas and 26% of persons carrying small adenomas had an abnormal ratio (> 1.0) of lithocholic acid to deoxycholic acid in intestinal contents as compared to 17% of the adenoma-free comparison group (n = 24). These findings support the suggestion that the ratio of lithocholic acid to deoxycholic acid as a faecal marker may be a useful adjunct to screening procedures for colorectal cancer.

Changes in the hepatic perfusion index during the growth and development of experimental hepatic micrometastases.

Micrometastases were induced in Fisher rats using an intraportal inoculation of 0.2 ml of 8 x 10(7) Walker carcinosarcoma cells. A control group received normal saline. The hepatic perfusion index (HPI) was measured during the growth and development of micrometastases. The HPI at 4 days (0.51 +/- 0.008) and at 6 days (0.65 +/- 0.16) was significantly raised when compared to controls (0.31 +/- 0.07) and at 2 days after inoculation (0.31 +/- 0.06). Hepatic artery flow did not change throughout the study period. However, portal venous inflow was decreased significantly at 4 and 6 days (0.57 +/- 0.16 and 0.55 +/- 0.11) when compared to controls (0.96 +/- 0.34). These results indicate that the change in the hepatic perfusion index is related to a decrease in portal venous inflow. The decrease in portal venous inflow could be a mechanical effect of the micrometastases on intrahepatic blood flow or to increased arteriovenous shunting.

The adenoma-carcinoma sequence.

The adenoma-carcinoma sequence refers to the development of malignant change in a precursor focal dysplastic polypoid lesion, the adenoma. In the intestinal tract of man this progression has been most clearly documented in the large bowel and although the evidence is largely circumstantial, it would appear that the majority of malignant tumours at this site arise in this way. By contrast this course is unusual in the stomach, the other major site of gut malignancy, where adenomas are uncommon. Small intestinal adenocarcinoma is rare but there is evidence that a significant proportion of these tumours develop from a precursor adenoma. In the large bowel, adenomas are very common lesions in those populations where there is a high incidence of colorectal cancer. The likelihood of malignancy developing in an adenoma is related to increasing size, a villous as opposed to a tubular growth pattern, and the severity of cytological and architectural abnormalities (dysplasia) of the epithelium.

The adenoma-carcinoma sequence.

Evidence has been presented to show that most carcinomas of the large bowel develop in an adenoma, and that the life history of this sequence, although variable, probably takes on average 10 to 15 years. However, when the absolute numbers of adenomas and carcinomas are compared, it is apparent that the transition is uncommon. On a statistical analysis the malignant potential of adenomas is related to their size, growth pattern, and degree of epithelial atypia. If the adenoma-carcinoma sequence is the norm, then a study of these criteria in adenomas at different sites in the colon and rectum would resolve the disparity in published series between the distribution of adenomas and carcinomas.

Herpes simplex oesophagitis.

A patient is described with oesophageal ulceration due to herpes simplex virus type I. The endoscopic, light, electron microscopic, and immunohistochemical appearances are described and the literature of this under-diagnosed entity is reviewed.

An intrapulmonary teratoma associated with thymic tissue.

A benign teratoma was removed by segmental resection from the upper lobe of the right lung in a girl aged 19 years. This is the twentieth case report of a teratoma occurring in the lung substance and is of special interest because of the identification of thymic tissue histologically. The significance of this in relation to the pathogenesis of intrathoracic teratoma is discussed.

Subnuclear vacuolated mucous cells: a novel abnormality of simple mucin-secreting cells of non-specialized gastric mucosa and Brunner's glands.

We report a novel abnormality affecting simple mucin-secreting cells of the glands of pyloric gastric mucosa and of Brunner's glands. Subnuclear vacuolated mucous cells show a distinctive appearance on haematoxylin and eosin staining. They are columnar cells of similar size to simple mucin-secreting cells, but have a central nucleus beneath which the cytoplasm has a uniform glassy eosinophilic appearance or contains a clear area. Subnuclear vacuolated mucous cells are found focally lining the lower third of pyloric gastric glands or in Brunner's glands, and may be mistaken for a form of metaplasia. Histochemically, the apical portion of the cell stains for neutral mucin, but the basal portion stains only weakly and variably for protein. Electron microscopy reveals that the basal portion consists of a large, single, membrane-bound vacuole, variably indented by the nucleus, and probably derived from either endoplasmic reticulum or the Golgi apparatus. The vacuole contains granular material which varies in electron density from cell to cell. The apical portion of the cell contains organelles similar to simple mucin-secreting cells. These appearances are highly suggestive of an abnormal accumulation of non-glycoconjugated mucus core protein. Although the cause of this is unknown, it was associated with the histological changes of chronic gastritis in 10 of our 12 cases.