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.

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.

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.

Organ pathology following mild hypothermia used as neural rescue therapy in newborn piglets.

The aim of this study was to assess the possible adverse effects of hypothermia, used as neural rescue therapy in a newborn piglet model. Sixteen newborn piglets were subjected to transient cerebral hypoxia-ischaemia by temporary occlusion of the carotid arteries and reduction of the fractional inspired oxygen to 0.12. On resuscitation 11 piglets were maintained normothermic (38.5-39.0 degrees C) and, in order to assess the cerebroprotective effect of hypothermia, 5 piglets were cooled to 35 degrees C for 12 h before normothermia was resumed. At 48 or 64 h following resuscitation the animals were sacrificed and the heart, left kidney, specimens of distal small bowel, lung and liver were removed and histologically sectioned. No microscopic abnormalities of the heart, bowel or lung were observed in hypothermic or normothermic animals. All kidney specimens were normal except one from the normothermic group. Abnormal liver pathology suggestive of hypoperfusion injury was found in 5 normothermic and 3 hypothermic piglets. There was no significant difference in the proportion of piglets with liver abnormality between the two groups. Mild hypothermia following cerebral hypoxia-ischaemia in the newborn piglet was not associated with an increased incidence of non-cerebral organ damage. The hepatic injury observed may be related to umbilical venous catheterisation and has potential relevance to neonatal intensive care.

Genetic instability in patients with metachronous colorectal cancers.

BACKGROUND: Nearly 7 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers several years later. A molecular marker that could identify patients susceptible to metachronous cancers would be of clinical importance. METHODS: Twenty-four colorectal cancers from 15 individuals with metachronous colorectal cancer were investigated for microsatellite instability at five loci by single stranded conformational polymorphism analysis. A control group of 14 colorectal cancers from individuals who had only developed one sporadic colorectal cancer each was analysed similarly. RESULTS: Microsatellite instability was demonstrated in 17 of 24 cancers from individuals with metachronous cancer compared with one of 14 cancers from individuals with a single colorectal cancer. CONCLUSION: These results suggest that testing for microsatellite instability may be useful in recognizing patients at high risk of developing metachronous colorectal cancers.

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.

Photodynamic therapy of a transplanted pancreatic cancer model using meta-tetrahydroxyphenylchlorin (mTHPC).

Pancreatic cancer is difficult to treat, even for tumours localized to the pancreas. Photodynamic therapy (PDT) is a non-thermal technique for producing localized tissue necrosis with light after prior administration of a photosensitizing drug and it could have a role in the local treatment of these cancers. We studied PDT in a transplanted cancer in the hamster pancreas using the photosensitizer mTHPC (meta-tetrahydroxyphenylchlorin). Fluorescence microscopy showed maximum levels of mTHPC in normal pancreas 2-4 days after sensitization and in tumour at 4-5 days. For PDT, animals were given 0.1 or 0.3 mg kg(-1) mTHPC and the tumour was treated at laparotomy 2 or 4 days later with red light (50 J at 650 nm, continuous or fractionated) delivered via a single fibre touching the tumour surface. The maximum zone of tumour necrosis (seen 3 days after PDT) was 8.7 mm in diameter with continuous irradiation, increasing to 12.4 mm with light fractionation (four equal fractions with 3 min between fractions). The main complication was sealed duodenal perforation, seen in 3 of 16 animals, probably due to inadequate shielding of the duodenum from the light. The duodenal problems seen in hamsters are unlikely to cause trouble in the much thicker human duodenum. PDT tumour necrosis in this animal model has now been shown with a range of photosensitizers, but mTHPC is attractive as it is likely to produce the largest volumes of necrosis around each treatment point with short light exposure times. This technique could have a role in the treatment of localized cancers of the pancreas in patients unsuitable for surgery and can now be considered for preliminary clinical trials.

Effect of methylprednisolone on the ulceration, matrix metalloproteinase distribution and eicosanoid production in a model of colitis in the rabbit.

This study has examined the response of a rabbit model of inflammatory bowel disease to methylprednisolone. Colitis was induced in the colon of rabbits with 40 mg trinitrobenzenesulphonic acid in 25% ethanol (TNBS). The effect of methylprednisolone (0.5 mg/kg/day) on the development of colitis was determined at one week, by examining the colon's macroscopic and microscopic appearance, the distribution of matrix metalloproteinases (MMPs) and by measuring eicosanoid production. Although there was no difference in the area of ulcerated colonic tissue in the treated and untreated TNBS animals, the increase in polymorphonuclear leucocytes was significantly reduced in TNBS rabbits given methylprednisolone. The only difference in the distribution of MMPs was a reduction in the number of polymorphonuclear leucocytes containing gelatinase B. The release of immunoreactive PGE2 and LTB4, but not 6-keto PGF1 alpha, was increased in the TNBS animals and was unchanged by methylprednisolone. These results show that methylprednisolone does not modify the injury produced by TNBS in this model despite reducing the infiltration of polymorphonuclear leucocytes. Hence it suggests that these cells do not contribute to the injury observed, are not the source of the eicosanoids and that gelatinase B is not required in the healing process in this model.

Non-invasive perinatal necropsy by magnetic resonance imaging.

BACKGROUND: AT present necropsy is done in less than 60% of cases of perinatal death in the UK, despite the value of the procedure to the bereaved parents and their doctors. This low rate reflects the difficulty in discussing the examination during the acute distress after the death of a baby, and the personal and religious objections of many parents to necropsy. We compared post-mortem magnetic resonance imaging (MRI) of the fetus with internal perinatal necropsy to assess whether MRI examination is a feasible option for the 40% of cases where consent for necropsy is not given or requested. METHODS: We examined 20 stillborn, miscarried, or aborted fetuses by MRI and necropsy. Scanning was done in a 1.5 T system, in accordance with our protocol, immediately before necropsy. The MRI and necropsy findings were compared to assess how much diagnostic information was obtained by each technique. FINDINGS: In eight of the 20 cases the two examinations were in total agreement about the abnormalities present. In eight cases the necropsy provided more detailed information than MRI examination, but in four cases the MRI information was more extensive than that obtained at necropsy. In two of the latter cases, abnormalities of the central nervous system were seen only on MRI. Thus, in 12 (60%) of the 20 cases studied, MRI had equivalent or better diagnostic sensitivity than internal necropsy examination; in 18 (90%) of the 20 cases the two examinations were of similar clinical significance. INTERPRETATION: MRI of the stillborn or aborted fetus provides non-invasive access to information previously available only from necropsy.

Fine needle aspiration (FNA) cytology of the breast: the influence of unsatisfactory samples on patient management.

FNA continues to play an important role in the management of patients with breast lesions. However, the reliability and efficiency of the FNA service depends heavily on the quality of the specimens. We have audited the rate of "inadequate FNAs' at intervals over the last 5 years and related our findings to the clinical expertise of the aspirator. We have also correlated the rate of inadequate FNAs with the percentage of patients who had an FNA preceding a definitive diagnosis of cancer. We report trends in the rate of inadequate samples, and subsequent diagnosis of cancer, over a 5-year period. The percentage of breast FNA samples reported as inadequate was 46.8% in 1988-89, falling to 20% in 1991-92 with the introduction of an FNA clinic, and rising to 30.6% in 1993. The rates of cancer following inadequate FNA were 15.7%, 16.1% and 4.2%, respectively, and the percentage of patients with cancer having a preceding inadequate FNA were 37.5%, 13.2% and 7.1%. Possible explanations for the apparent paradox between increasing numbers of inadequate FNA specimens and a falling breast cancer rate are discussed.

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.

Deregulation of cell survival in cystic and dysplastic renal development.

Various aberrations of cell biology have been reported in polycystic kidney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine nephrogenesis, where it has been implicated in morphogenesis, and fulminant apoptosis occurs in the small, cystic kidneys which develop in mice with null mutations of bcl-2. Therefore, we examined the location and extent of apoptosis in pre- and postnatal samples of human polycystic and dysplastic kidney diseases using propidium iodide staining, in situ end-labeling and electron microscopy. In dysplastic kidneys cell death was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apoptosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was widespread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epithelia. The level of apoptosis compared to controls was significantly increased postnatally. A similar increase of cell death was also noted in the early and late stages of renal disease in the polycystic cpk/cpk mouse model. We speculate that deregulation of cell survival in these kidneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic kidneys.

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.

The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.

Lactase activity is present at high levels in the small intestine of some human adults and not others. This is due to a genetically determined polymorphism which affects the developmental regulation of the expression of the lactase gene. This polymorphism is of considerable interest in relation to cultural differences in nutrition but despite exhaustive studies, the molecular basis has not yet been found. It has not even been shown whether the sequence differences reside within or adjacent to the lactase gene itself or in a trans-acting factor. We have therefore exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans. Our results show that in certain lactase persistent individuals one allele of the lactase gene is expressed at much lower levels than the other and these individuals tend to have intermediate lactase activities. It is proposed that these people are heterozygous for the lactase persistence and non-persistence alleles and that this means that the nucleotide substitutions responsible for the lactase persistence/non-persistence polymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differences.