Changes in gene expression in established human mammary tumor cell lines when compared with normal breast and breast tumor tissue.

RNA complexity analyses of total cellular polyadenylate-containing RNA isolated from lactating human breast tissue, human breast tumor tissue, and a mixture of established cell lines of mammary origin demonstrate extensive homology between the tissue RNA populations but suggest a decrease in the complexity of cell line nuclear RNA populations, with the exception of an early-passage MCF-7 cell line. Cell-free protein synthesis and two-dimensional gel electrophoresis also show quantitative and qualitative differences in gene expression between human mammary tumor tissue and reduction mammoplasty or established mammary cell lines of early and late passage number. The results demonstrate a major role for transcriptional and posttranscriptional mechanisms in the regulation of gene expression in the human mammary gland and show that studies on mammary gland gene expression using established cell lines of mammary origin reflect only in part gene expression in normal lactating human breast or breast tumor tissues.

Is massage following dye injection necessary in sentinel node biopsy in breast cancer?

In sentinel node biopsy of breast cancer, massaging of the dye injection site following subdermal injection of blue dye does not improve sentinel node detection rate or the time needed for sentinel node biopsy. It may reduce the number of false negative sentinel nodes.

Imprint cytology of the sentinel lymph node in the assessment of axillary node status in breast carcinoma.

BACKGROUND: Intra-operative assessment of the sentinel lymph node (SLN) status may allow the surgeon to complete the breast cancer surgery in most patients in one sitting. We have studied the role of imprint cytology in the assessment of SLN status. PATIENTS AND METHODS: Imprint cytology of the SLN in 132 patients with invasive breast carcinoma was correlated with the histopathological assessment of the SLN and overall axillary nodal status. In 26 patients, the cytology was reported intra-operatively. RESULTS: Imprint cytology reflected the status of the parent node well (sensitivity 86%, specificity 97%, positive predictive value (PPV) 92%, negative predictive value (NPV) 93%). Its ability to reflect the axillary status was also good (sensitivity 70%, specificity 97%, PPV 95% and NPV 83%) but somewhat diminished by the relatively high number of false-negative SLN in the study. Intra-operative assessment (sensitivity 86%, specificity 100%, PPV 100% and NPV 95%) did not reduce the accuracy of imprint cytology in predicting the SLN status and took a mean of 24.5 min. CONCLUSIONS: Imprint cytology is an accurate and relatively simple method for the assessment of the SLN and can be a useful intra-operative tool.

Is the undeniably palpable liver ever 'normal'?

A study of whether the lower border of the normal liver, if it extended below the costal margin, could be reliably identified by clinical examination was undertaken in 42 patients in whom there was no clinical, biochemical or scintographic evidence of liver disease. Two clinical observers independently agreed that in 10 of these patients the liver extended infracostally. However, scintiscanning demonstrated that 30 patients had livers extending below the costal margin and that 2 of the 10 livers clinically identified did not in fact lie infracostally. Thus whilst the normal liver commonly extended below the costal margin, recognition of this extension by clinical methods occurred no more frequently than would be expected by chance. It is concluded that the confident clinical finding of a liver projecting below the costal margin should suggest that the organ is abnormal.

An aetiology for fistula in ano.

Four cases of superficial peri-anal fistula occurring in early infancy are described. They were all successfully treated by complete excision of the fistula. Histological examination of the excised fistulae revealed a mixture of columnar, transitional and stratified squamous epithelium lining the tracts in three cases and non-specific connective tissue in the fourth. It is postulated that the presence of these inappropriate types of epithelium (columnar and transitional) along the length of the fistulous tract is evidence of a congenital origin for peri-anal fistulae presenting in the first few months of life.

Gastric emptying and dumping after proximal gastric vagotomy.

One hundred dumping provocation tests were performed on patients who had had proximal gastric vagotomy without drainage in the pre- and postoperative period. Other than monitoring the symptoms of dumping on test, various other objective criteria, i.e., plasma volume fall, gastric emptying, and blood sugar changes were also measured simultaneously. Whether dumping was assessed clinically or on test, it seemed to be equally prevalent after proximal gastric vagotomy without drainage compared to vagotomy with drainage or partial gastrectomy. Although the pattern of gastric emptying after proximal gastric vagotomy alone was not significantly different from that before operation in those patients who had dumping symptoms on test, the half-life of the emptying were much faster. The plasma volume fall was also significantly greater and blood sugar was rise steeper in these patients. The objective measurements have not only helped in determining the incidence of dumping after proximal gastric vagotomy but have also proved to be of value in categorizing patients with doubtful symptoms and have given some insight into the etiopathogenesis of this syndrome.

The synthesis of 16 alpha-[131I]iodo-oestradiol and evaluation of its use as a radiotracer for oestrogen receptor positive breast tumours.

16 alpha-Iodo-oestradiol binds with high affinity to the oestrogen receptor and has been shown to accumulate in oestrogen sensitive tissues in many test systems. We have prepared the compound labelled with 131I at four specific activities. Using these preparations we have attempted to image human primary and metastatic breast cancer deposits at various times from 15 min to 24 h post injection by external gamma scintigraphy. Clinical studies were conducted on 10 post-menopausal patients. The receptor status was determined in seven cases, four were positive and three negative. The imaging results were very poor, in only two cases were images obtained, these were very faint and only of the primary, never of the metastatic deposits. The oestrogen receptor status was only available in one of these cases, it was positive. Dynamic studies in vivo revealed that the compound is cleared rapidly from the circulation during the first 5 min and thereafter undergoes extensive enterohepatic recycling. Studies of the radiochemical identity of the circulating species revealed that the injected compound was extensively metabolised. Neither an increase in specific activity of injected radiotracer nor imaging at shorter times after injection improved the results.

Skin closure of inguinal herniorrhaphy wounds in short-stay patients.

One hundred and twenty-two inguinal hernias were repaired in a consecutive series of 104 patients. The patients were randomly divided into two groups. In one, 66 wounds were closed by the traditional method of using interrupted non-absorbable skin sutures. In the second group, 56 wounds were closed with subcuticular Dexon sutures. The results of the two methods of skin closure were compared in the immediate postoperative period, at 2 weeks, 3 months and at more than 18 months after surgery. The final appearance of the wounds was similar in the two groups. Dexon has the advantage for short-stay patients of not requiring removal.

Influences on the occurrence of dumping syndrome.

A dumping provocation test using 50% of glucose solution labeled with Indium 115 m, was performed on 146 occasions pre- and postoperatively in 85 patients. Dumping elicited by the test was defined by the symptoms produced by the test and various objective measures of dumping. The influence of various factors other than the type of operation on the occurrence of dumping has been studied in detail. The incidence of dumping symptoms induced by the test has shown no significant correlation with age, sex, weight, height, smoking habits, race, dose of hypertonic glucose, and the time elapsed since surgery. However, a significant relationship has been observed between the duration of ulcer symptoms before operation and the occurrence of dumping symptoms induced by the test. The test not only reproduced the symptoms patients had reported after eating ordinary foods, it also helped in eliminating patients with borderline symptoms as our objective measures collectively differentiated three patients from those with the dumping syndrome.

Iatrogenic gastrocolic fistula associated with non-steroidal anti-inflammatory drug administration.

An unusual case is presented of a benign gastrocolic fistula occurring in a 70-year-old man treated with piroxicam for arthritis for a period of only two months. This report illustrates that significant upper gastrointestinal complications can occur, even with short-term treatment, with non-steroidal anti-inflammatory drugs (NSAIDs).

In situ hybridisation and S1 mapping show that the presence of infiltrating plasma cells is associated with poor prognosis in breast cancer.

In order to identify potential markers of prognosis in breast cancer, representative cDNA libraries were constructed using RNA isolated from primary breast tumour tissue associated with good and poor prognosis. Cross-screening of these libraries repeatedly identified cloned mRNA species associated with the immune system, in particular B-cells, in libraries derived from tumours of poor prognosis. We have used one of these a kappa IV light chain cDNA probe, in two complementary studies to investigate the relationship between immunoglobin gene expression and prognosis. The results obtained using a combination of S1 mapping, RNA blotting and in situ hybridisation demonstrate that the presence of plasma cells, as defined by infiltrating cells which express high levels of immunoglobulin kappa-chain mRNA, is associated with a poor prognosis.

Colonic tuberculosis presenting with massive rectal bleeding.

Colonic tuberculosis manifests in many diverse ways, of which massive rectal bleeding is a rare feature requiring surgical treatment by resection. We report such a case and review the literature of the last 15 years.

Use of a provocation test for objective assessment of dumping syndrome in patients undergoing surgery for duodenal ulcer.

It is difficult to assess the incidence of dumping after various operations for duodenal ulcer on clinical grounds alone. An objective assessment of dumping has been made with the help of a provocation test. The test, using 50% hypertonic glucose solution labeled with radioactive Indium 113m was performed on 39 preoperative patients and 107 times on 72 patients after operation for duodenal ulcer. The dumping status of all the patients prior to surgery was asymptomatic after ordinary food as well as on test. Among the postoperative studies the clinical status was asymptomatic in 69, uncertain in 32 and six had dumping symptoms. On the basis of the symptoms on-test, the status was asymptomatic in 61, uncertain in 14 and 32 had dumping symptoms. The objective indices further defined the status as 70 asymptomatics, none uncertain and 37 confirmed dumpers and thereby completely abolished the uncertain group. All the objective measurements of the dumping provocation test have clearly differentiated those patients with from those without dumping symptoms. Patients with dumping symptoms on-test had a significantly greater fall in plasma volume, more rapid rates of gastric emptying and steeper rise in blood sugar after ingestion of hypertonic glucose than did the patients without dumping symptoms on-test.

Pectin in the dumping syndrome: reduction of symptoms and plasma volume changes.

Twelve patients with the dumping syndrome took on one occasion oral hypertonic glucose and on another a similar glucose drink to which pectin was added. After glucose alone eleven patients had symptoms; after glucose with pectin, six had no symptoms and in five symptoms were reduced. Plasma volume changes were significantly less after glucose with pectin, and the hypoglycaemia at 120 min after glucose alone did not occur after glucose with pectin in patients in whom symptoms were abolished. Gastric emptying was prolonged, and serum insulin levels were lower, after glucose with pectin. In those patients to whom gastric emptying rate reverted to near normal with pectin, symptoms were abolished, but symptoms were only reduced in number when gastric emptying, although slowed, remained rapid. The findings suggest that pectin and similar substances may be useful in the day-to-day management of patients with dumping symptoms.

How accurately can direct and indirect inguinal hernias be distinguished?

An inguinal hernia was clinically diagnosed as direct or indirect by paired surgeons of 134 occasions. When compared with the findings at operation the hernia was correctly diagnosed in 60 of 78 observations when it was indirect and in 33 of 56 when it was direct. The level of accuracy does not warrant continuing the practice of attempting to distinguish one type of inguinal hernia from another.

alpha-Lactalbumin is not a marker of human hormone-dependent breast cancer.

It has been proposed that milk protein gene expression in human breast carcinomas may indicate a functional oestrogen receptor mechanism, and may therefore be diagnostic of tumours responsive to endocrine therapy. Unfortunately this has not been proved, largely because of inconsistencies in the immunoassay procedures used to identify milk proteins, in particular alpha-lactalbumin, in tissue extracts or serum. Alternative procedures include the identification of milk protein mRNA by cell-free protein synthesis, and the identification of milk protein RNA transcripts by hybridization to a sequence-specific probe. Here we describe experiments using alpha-lactalbumin cDNA probes, purified using recombinant plasmids, which demonstrate that although polyadenylated and non-polyadenylated alpha-lactalbumin transcripts are present in normal human mammary tissue during pregnancy and lactation, alpha-lactalbumin transcripts are not detectable in the human tumour tissues studied. These experiments do however show that a peptide, which shares antigenic determinants with human alpha-lactalbumin is present in some breast tumour tissues.