The PAX2 tanscription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations.

Human dysplastic kidneys are developmental aberrations which are responsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to metaplastic elements. We recently demonstrated that apoptosis was prominent in undifferentiated cells around dysplastic tubules (Winyard, P.J.D., J. Nauta, D.S. Lirenman, P. Hardman, V.R. Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps explaining the tendency of some of these organs to regress. In contrast, apoptosis was rare in dysplastic epithelia which are thought to be ureteric bud malformations. On occasion, these tubules form cysts which distend the abdominal cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely become malignant. We now demonstrate that dysplastic tubules maintain a high rate of proliferation postnatally and that PAX2, a potentially oncogenic transcription factor, is expressed in these epithelia. In contrast, both cell proliferation and PAX2 are downregulated during normal maturation of human collecting ducts. We demonstrate that BCL2, a protein which prevents apoptosis in renal mesenchymal to epithelia] conversion, is expressed ectopically in dysplastic kidney epithelia. We propose that dysplastic cyst formation may be understood in terms of aberrant temporal and spatial expression of master genes which are tightly regulated in the normal program of human nephrogenesis.

Postmortem magnetic resonance imaging as an adjunct to perinatal autopsy for renal-tract abnormalities.

The aim of this study was to compare postmortem magnetic resonance imaging (MRI) of the renal system with autopsy in perinatal and fetal deaths. 37 deaths were studied and renal abnormalities were found in five of these cases. Postmortem MRI provided information of diagnostic utility comparable to that obtained by autopsy.

Unusual lymphangioma observed prenatally in a 45,X fetus.

We present a case of a large frontal lesion, suspected on antenatal ultrasound to be a cephalocele. The cardiac anatomy was abnormal and fetal blood sampling showed a 45,X chromosome constitution. Postmortem examination proved this to be a lymphangioma and confirmed the presence of a cardiac defect. We suggest that this lymphangioma represents an unusual manifestation of monosomy X and discuss the importance of doing chromosome analysis in the presence of such a lesion which is of similar appearance as a cephalocele.

Abdominal malignancies in patients with Wilson's disease.

BACKGROUND: Wilson's disease is associated with heavy copper overload, primarily in the liver. Copper is a toxic metal, and might be expected to be associated with cancer induction, as iron is in haemochromatosis. However, liver cancer is currently believed to be extremely rare in this disease, and other intra-abdominal malignancies have not been reported. AIM: To assess the frequency of abdominal malignant disease in patients with Wilson's disease on long-term follow-up. DESIGN: Retrospective study in two specialist Wilson's disease clinics: Cambridge/London and Uppsala. METHODS: We reviewed the case records of 363 patients seen at three centres: Addenbrooke's Hospital, Cambridge, 1955-1987; the Middlesex Hospital, London, 1987-2000; and the University Hospital, Uppsala, Sweden, 1966-2002. Patients were grouped by length of follow-up: 10-19 years; 20-29 years; 30-39 years; and 40 years or more. RESULTS: No cancers were seen in patients followed for <10 years. For patients in the 10-19 years group, the frequency was 4.2%; at 20-29 years, it was 5.3%; and at 30-39 years, 15%. No cancers were seen in the 40+ years follow-up group. The cancers consisted of hepatomas, cholangiocarcinomas, and poorly differentiated adenocarcinomas of undetermined primary site. DISCUSSION: Patients with Wilson's disease appear to be vulnerable to the formation of aggressive malignant intra-abdominal tumours during long-term follow-up, irrespective of treatment. Ultrasound scanning of the abdomen seems to be a useful screening procedure.

Risks and benefits of percutaneous biopsy and primary chemotherapy in advanced Wilms' tumour.

Between 1982 and 1988, 36 children with advanced Wilms' tumour underwent percutaneous trucut needle biopsy followed by chemotherapy before definitive surgery. Nephrectomy was performed after a median of 14 weeks of chemotherapy. Substantial reduction in tumour bulk was achieved in 94% of patients. Biopsy morbidity was low and complete concordance between the histological assessment of the tumour in the biopsy specimen and at subsequent nephrectomy was confirmed in 26 of 28 (93%) patients. The overall clinical value of trucut biopsy was 83% (30/36 patients). Survival rates in this high-risk group were comparable to those of children with less advanced disease. Chemotherapy may be the primary treatment of choice for patients with Wilms' tumour. Percutaneous biopsy allows definition of histology in most patients without increasing morbidity.

Ectopic pancreas. A cause of false-positive peritoneal cytology.

A patient with a history of ovarian adenocarcinoma underwent further surgery because malignant cells were reported in peritoneal washings on two separate occasions. Subsequent laparotomy revealed an ectopic pancreas on the jejunum. Review of the peritoneal cytologies confirmed that the cells previously thought to be malignant were in fact consistent with cells detached from the ectopic pancreas.

Treatment of severe self-injurious and aggressive biting.

The treatment of a 16-year-old severely mentally retarded and blind female client exhibiting severe biting of self and others consisted of the contingent application of an aversive gustatory stimulus (Tabasco Sauce), brief timeout, DRO, and contingent restraint against biting while in time-out. This is the first use of Tabasco as the aversive stimulus against biting. Deceleration of biting was rapid and maintained for 20 months after initiation of treatment.

Angiosarcoma of the right atrium presenting as syncope and hemorrhagic pericardial tamponade.

Angiosarcoma of the heart is a rare malignancy that can present in many ways. It is an important diagnosis to consider in patients presenting with otherwise unexplained tamponade-type symptoms. Here we present a case of a young male who presented with hemorrhagic tamponade and underwent resection of a large angiosarcoma of the right atrium. In this case, we describe the rare presentation of angiosarcoma with its diagnostic approaches, hospital course, clinical management, and discussion.

Severe tracheobronchomalacia after prolonged intubation of multitrauma patient.

Tracheobronchomalacia is a condition with significant morbidity with many etiologies including iatrogenic ones and should be considered in critically ill ventilated trauma patients. We present a case of a multitrauma patient who had difficulty weaning from the ventilator after prolonged intubation followed by tracheostomy tube placement. We describe her presentation, diagnosis, and management provide and as well a discussion of the condition.

The effects of gemeprost on the second trimester fetus.

OBJECTIVE: To determine whether the use of gemeprost is associated with histological changes in the second trimester fetus. SETTING: Histopathology department of a university hospital. DESIGN: Retrospective comparison of histological features in fetuses aborted following maternal administration of gemeprost, with those in fetuses after spontaneous miscarriage. OUTCOME MEASURES: Degree of tissue fragmentation; other histological abnormalities. RESULTS: Significantly greater fragmentation of the liver was found in fetuses exposed to gemeprost (P = 0.046). Nonsignificant effects were found for brain (P = 0.082) and heart (P = 0.183), and no effect was seen on the kidney, adrenal and lung. No other significant histological differences were found between the two groups. CONCLUSIONS: This study is the first to document an effect of gemeprost on the fetus, but confirmation is required in further studies. Other implications are discussed.

The characterization of a rabbit model of inflammatory bowel disease.

The absence of a simple, clinically relevant, animal model of inflammatory bowel disease (IBD) hampers research into this disease. In this study, colitis was induced in rabbits by intracolonic installation of 2,4,6-trinitrobenzene sulphonic acid (TNB) in 25% ethanol. Rabbits were killed from zero hours to 6 weeks and their colons examined. Rabbits were examined by endoscopy at weekly intervals. A single dose of TNB in ethanol produced dose dependent inflammation and ulceration, which at its optimum (40 mg) resulted in cobblestoning, strictures, and bowel wall thickening. The damage score at endoscopy was consistent with the score on macroscopic examination of the colon. Histopathological features of inflammation and ulceration observed in all animals that received 40 mg TNB included crypt abscesses, ulceration, crypt architectural distortion and, occasionally, granulomas and pseudopolyps. These changes, which are similar to those observed in IBD, persisted for 6 weeks. No lasting abnormalities were observed in control animals treated with TNB in saline, with ethanol alone, or with saline only. Histopathological similarity and the prolonged duration of inflammation, compared to other models, make this a suitable model for investigating inflammation in the colon. Furthermore, the model is accessible to endoscopy which adds to its value in experimental studies.

Albuterol and nedocromil sodium affect airway and leukocyte responses to allergen.

We investigated the effects of inhaled nedocromil sodium and albuterol administered prior to allergen challenge in the late asthmatic response (LAR) and circulating cells in a double-blind placebo-controlled study. An additional control day (no allergen) was included to determine diurnal variation. On the control day no change in airway caliber occurred, but a diurnal increase in the numbers of all circulating leukocytes except basophils was seen. Placebo premedication followed by allergen challenge caused both an early asthmatic response (EAR) and a late asthmatic response (LAR). Following allergen challenge after placebo the diurnal increase in eosinophils at 8 h was abolished, and elevated eosinophil and basophil counts were observed at 24 h. Nedocromil sodium attenuated both the EAR and the LAR, and it restored the eosinophil and basophil responses toward normal. Albuterol abolished the EAR and attenuated the LAR and the 24-h increase in circulating basophils. No changes in lymphocyte subpopulations were seen. We conclude that during the LAR there is entrainment of eosinophils within the lung, with a subsequent bone marrow response increasing peripheral populations of eosinophils and basophils. Nedocromil sodium may act by inhibiting the recruitment of inflammatory cells, particularly eosinophils, possibly by affecting the generation of cytokines and the expression of leukocyte-specific adhesion molecules. Albuterol may have similar actions as shown by an effect on basophils.

Comparative study of carcinoembryonic antigen and epithelial membrane antigen expression in normal colon, adenomas and adenocarcinomas of the colon and rectum.

The heterogeneous nature of tumour antigen expression may require selection of monoclonal antibodies on an individual patient or tumour basis to allow adequate tumour localisation. Carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression has not previously been compared in colorectal cancer patients. Sections of cancer (n = 52), adjacent normal colon (n = 45), synchronous adenomas (n = 11) and nodal metastases (n = 49) were examined by indirect immunoperoxidase staining in 51 consecutive patients with colorectal cancer using monoclonal antibodies to CEA and EMA. The percentage of cells with positive staining in the primary tumours was graded 1: less than 25%, 2: 25-49%, 3: 50-75%, 4 greater than 75%. All primary colorectal cancers expressed CEA and 43 of 52 expressed EMA (83%). Grading showed CEA greater than EMA in 39, equal in 11 and less in two. Well differentiated cancers were more frequently graded three or four for CEA staining (23 of 27) than moderately differentiated cancers (11 of 22) (p less than 0.01). Equivalent figures for EMA were four of 27 and three of 22 (not significant) (NS) although the majority (86%) were graded 1 and 2. Grade 1 CEA expression was found in six of 15 proximal and only two of 37 distal lesions (p less than 0.01, chi 2 test) while for EMA equivalent figures were three of 15 and six of 37 (NS). Nodal deposits all expressed CEA and 45 of 49 expressed EMA (92%); 29 of 45 normal colon sections showed CEA expression (64%) as did all adenomas. EMA was not expressed by normal colon or adenomas. These results suggest that EMA expression is more specific but less sensitive than CEA for colonic cancer and is independent of tumour differentiation and site. Thus selecting monoclonal antibodies to CEA or EMA based on tumour biopsies may allow improved tumour localisation for imaging or therapy in patents with colorectal cancer.

Nephrogenic rests and renal abnormalities in Brachmann-de Lange syndrome.

We report renal abnormalities found in four cases of Brachmann-de Lange syndrome (BDLS). In two there were nephrogenic tests and renal cortical cysts, a further case showed cortical cysts, and the fourth had dilated collecting ducts. The literature describing renal abnormalities in BDLS has been reviewed, and this includes a report of one individual with BDLS who developed Wilms tumor. The genetic basis of BDLS has not been elucidated, although a submicroscopic abnormality of chromosome 3 seems likely. Nephrogenic rests may be Wilms' tumor precursor lesions and are seen in syndromes associated with Wilms' tumors. Mutations of genes on chromosome 11 are the most common genetic abnormalities associated with Wilms' tumor, but other chromosomes have also been implicated. The frequency of renal abnormalities in the BDLS suggests that the involved gene may be important in renal development and also possibly in Wilms' tumors.

Detection of occult nodal metastases in patients with colorectal carcinoma.

Immunohistochemical study may be used for detecting micrometastases by their expression of tumor-associated antigens. In 48 specimens of colorectal cancer from 47 patients, 49 of 249 lymph nodes (median, five per patient; range, 2-11) examined by light microscopic study contained tumor deposits. Sections of all lymph nodes were also examined by immunohistochemical study for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression using the indirect immunoperoxidase staining method. All 49 lymph node metastases (100%) from 20 patients stained positively for CEA and 45 (92%) expressed EMA. Of the 200 lymph nodes without metastases on light microscopic examination, anti-CEA revealed a single micrometastasis in a patient staged as Dukes' B. No additional metastases were detected with anti-EMA. In this series of patients immunohistochemical study has, therefore, influenced the histologic staging in only one patient (2%) and thus does not offer a significant benefit over conventional histologic staging.

Disseminated porokeratosis in an infant with craniosynostosis.

An infant with craniosynostosis and other congenital defects developed a progressive skin rash from the age of 1 month. Histological examination revealed dyskeratosis and a cornoid lamella suggestive of porokeratosis. This patient is remarkable for the early onset and severity of the skin disease.