Papillary carcinoma in a male breast cyst: a diagnostic challenge.

Intracystic papillary breast carcinoma is a rare form of non-invasive carcinoma with an excellent prognosis. It accounts for less than 0.5% of breast cancers. We report the case of a 75-year-old man presenting with a painless cystic lump in the right breast. Ultrasonography showed a cystic lesion and aspiration revealed blood-stained fluid with suspicion of malignancy. Excisional biopsy was necessary to confirm the diagnosis and also indicated that local treatment was adequate.

Wegener's granulomatosis involving prostate.

We report a rare case of Wegener's granulomatosis involving the prostate in a 28-year-old man. The initial medical treatment was effective, but surgical intervention was required to manage late complications.

Measurement of liver fat by MRI and its reduction by dexfenfluramine in NIDDM.

OBJECTIVE: To validate a variation of a well-established magnetic resonance imaging (MRI) technique to detect liver fat and use it to monitor liver fat changes after treatment with dexfenfluramine in men with non-insulin dependent diabetes mellitus (NIDDM). DESIGN: (a) Simple correlation study of MRI Liver Fat Index with liver biopsy results; (b) Open Study of 10 men with NIDDM treated with dexfenfluramine for 12 weeks in addition to their 'usual' therapy. SUBJECTS: (a) 19 patients (3F; 16M) with abnormal liver function tests undergoing liver biopsy; (b) 10 men, Body Mass Index (BMI) < 30, Waist to hip ratio (WHR) > 0.90 with poorly controlled NIDDM despite oral sulphonylurea therapy. MEASUREMENTS: (a) MRI liver fat; standard liver biopsy; (b) MRI visceral fat, MRI liver fat, euglycaemic clamp, plasma lipids, fasting glucose and c-peptide levels. RESULTS: In the validation group, there was a strong relationship between the MRI Liver Fat Index and histopathological assessment of the liver biopsies (r = 0.87, < 0.0001). During treatment with dexfenfluramine the mean Liver Fat Index reduced from 10.6 +/- 3.4 to 6.6 +/- 2.8 (P = 0.05). The reduction in Liver Fat Index correlated with the reduction in visceral fat (r = 0.84, P = 0.001) as well as with the improvement in insulin sensitivity (r = 0.62, P = 0.05). Using partial correlation analysis, the relationship between the change in visceral adipose tissue and the improvement in insulin sensitivity was weaker if the Liver Fat Index was kept constant (r = 0.76 decreased to r = 0.56). CONCLUSIONS: In this group of subjects MRI Liver Fat Index correlated well with liver fat as seen on biopsy. The Liver Fat Index reduced after 12 weeks therapy with dexfenfluramine suggesting a role for hepatic steatosis in the complex interaction between visceral adipose tissue and insulin sensitivity.

Merkel cell carcinoma of the pinna.

Merkel cell carcinoma is an increasingly recognized tumour of the skin. The commonest presentation is the head and neck region. Only three cases of this rare tumour have been reported on the pinna. A further such case is presented here.

Focal destructive cholangiopathy associated with amoxycillin/clavulanic acid (Augmentin).

Amoxycillin/clavulanic acid (Augmentin) has been widely used as a broad spectrum antibiotic since its introduction in 1981, since which time a number of reports of adverse hepatic reaction to the drug combination have been published. This paper describes five patients presenting with cholestatic illness within 8 weeks of a course of amoxycillin/clavulanic acid. The clinical picture indicated a direct link between the illness and the drug combination. Hepatic histology revealed a distinctive focal destructive cholangiopathy in all five patients, which has not previously been reported. Two also showed a granulomatous reaction, which has only previously been reported in one patient. Parallels are drawn with other diseases displaying bile duct destruction, and it is suggested that immunologically mediated drug-induced biliary damage may be involved. One of the five patients developed chronic liver disease with persistence of cholestatic liver biochemical tests, which has not previously been reported. The severity of the reaction and its prolonged course merit wider recognition of the possible adverse hepatic reaction to amoxycillin/clavulanic acid.

Problems associated with using in vivo proton (1H) magnetic resonance spectroscopy to quantify liver fat.

In-vivo 1H magnetic resonance (MR) spectra of the liver were obtained in 8 patients admitted for liver biopsy. These patients had abnormal liver function and the presumptive diagnosis of fatty liver prior to biopsy. Two patients with NIDDM were also studied but liver biopsies were not performed as liver function was normal. The MR spectra, obtained on a 60 cm clear-bore 1.9 tesla superconducting magnet showed two 1H resonances, one from water and the other from repeating methylene protons - (CH2)n - in triglyceride. The lipid: water signal ratio was used to characterize tissues as subcutaneous fat (high lipid:water ratio), normal liver (low lipid: water ratio) and fatty liver (intermediate lipid: water ratio). The spectra obtained at the greatest depth from the probe surface ~4.5 cm) was used as it was most likely to represent liver tissue. Although all 8 patients were expected to have fatty liver only 2 had evidence of significant fatty changes on microscopy. This was assessed by counting the vacuoles of fat over the area of the biopsy specimen and quantitated as 'fat vacuoles per high power field' (f/hpf). In the 2 patients with NIDDM, unusual stack plots suggested technical difficulties with 1H MR spectroscopy for in-vivo assessment of fatty liver. The first patient, PT had a significant increase in lipid:water ratio on the spectra thought to represent liver (lipid:water ~ 65% cf levels <3% in norma liver and 12.6% + 26.5% in those patients subsequently found to have fat on biopsy). This was later found on MR imaging to represent omental fat lying between the liver and muscle layer. The second patient, OM had a large amount of subcutaneous fat overlying the area assessed. As seen on the stack plot, the probe depth was not great enough to pass through the subcutaneous fat and muscle layer to penetrate liver tissue. There was a significant correlation between the lipid:water signal ratio and visible fat on biopsy in those patients who underwent liver biopsy. Difficulties experienced with probe depth suggests imaging would be necessary prior to spectroscopy to ensure liver tissue is actually assessed.

Dextropropoxyphene induced hepatotoxicity: a report of nine cases.

Nine patients are described with jaundice, upper abdominal pain and malaise attributable to dextropropoxyphene hepatotoxicity. In each case the history was suggestive of large bile duct obstruction. All patients underwent ultrasound examination and percutaneous liver biopsy. Three patients also underwent endoscopic retrograde cholangio pancreatography. The histological features of the biopsies concur with previously reported cases of dextropropoxyphene hepatotoxicity. The histological changes seen on biopsy were remarkably constant, consisting of centrilobular cholestasis, portal tract inflammation and bile duct abnormalities, in all cases mimicking large bile duct obstruction. Fifteen previous patients with probable dextropropoxyphene hepatotoxicity have been described. The occurrence of 9 further cases at one centre, 6 presenting within 12 months, suggests that it is much more common than previously assumed and may be misdiagnosed as large bile duct obstruction.

Comparison between liver and serum concentrations of mannan binding protein.

AIMS: To investigate staining patterns for mannan binding protein (MBP) by immunocytochemistry in liver biopsy specimens from patients with various hepatic disorders; to measure the serum MBP concentration in the patients at the time of biopsy; and to compare these to define further the role of MBP in disease. METHODS: Fifty seven consecutive patients with a variety of types of liver disease were studied. Fresh liver biopsy specimens were immunostained with anti-MBP and graded for intensity of staining. Serum MBP concentrations were measured on samples obtained on the day of biopsy, as were a full range of liver blood tests. RESULTS: MBP was only detectable in liver biopsy specimens from patients with morphological evidence of liver disease. MBP was most prominent in the livers of patients with severe alcoholic liver disease; livers harbouring metastases or showing biliary disease had moderate concentrations. Patients with liver disease were more likely to have raised serum MBP concentrations, but there was no correlation between these values and those found in the biopsy specimens. There was also no significant correlation between either of these concentrations and liver blood test abnormalities. CONCLUSIONS: Patients with liver disease tend to have raised MBP concentrations in both the liver and serum, but the exact relation between the two is as yet undefined.

Co-expression of markers for hepatitis delta and hepatitis B viruses in human liver.

Delta hepatitis (HDV) infection can only occur in the presence of hepatitis B (HBV) infection, as HDV requires a coat of HBV surface antigen (HBsAg) for assembly of complete virus. A number of studies have examined the variation of HBV markers in serum and liver during establishment of HDV infection, but none has systematically examined the relationship between the two viruses in individual hepatocytes. Liver biopsies from five patients with HDV/HBV infection were stained for HBsAg, HBV core antigen (HBcAg) and hepatitis D (delta) antigen (HDAg). Double immunostaining was performed with a combination of indirect immunoperoxidase and alkaline phosphatase/antialkaline phosphatase techniques. HDV and HBV antigens were expressed in all five liver biopsies. Co-localization of HBsAg was seen in up to 39% of HDAg positive cells, and HBcAg in up to 8% of HDAg positive cells. HBcAg was detectable in approximately 9% of HBsAg positive cells, and HBsAg in approximately 12% of HBcAg positive cells. HDV can replicate without HBV but ultimately requires HBV to produce complete virus and subsequently infect other cells. In this study the majority of HDV positive cells did not appear to contain HBV markers. This might suggest delta virus replication without assembly, or possibly sequential production/assembly of the virus.

Mannan-binding protein in human liver.

Mannan-binding protein (MBP) is a Ca(2+)-dependent lectin which was first described in 1978 in rabbit liver, and subsequently in serum and liver tissue from humans and a range of animal species. MBP structurally resembles C1q, and may act both as a focus for complement activation on the surface of microorganisms and as an opsonin in its own right. Low serum levels of serum MBP have been described in a group of children known to suffer from severe recurrent infections. MBP has also been reported to behave as an acute phase reactant. This preliminary study has investigated the localisation of MBP in human tissues using material obtained both at post mortem and from diagnostic liver biopsies. Using the IgG fraction of rabbit anti-human MBP, immunoperoxidase staining showed no evidence of significant MBP in a wide range of normal tissues, including liver taken both at post mortem and needle biopsy. However, there was a significant degree of staining for MBP in liver biopsies showing a variety of different pathologies, in particular severely damaged alcoholic livers, and those harbouring metastatic tumour. Moderate degrees of staining were also seen in liver biopsies from patients suffering from chronic biliary disease. It is uncertain whether this localisation of MBP in abnormal liver is an acute phase response, or represents a more fundamental link with liver disease. This question could be the focus for future studies.

Liver abnormality in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a potentially fatal condition associated with the therapeutic induction of ovulation in infertility. Liver function abnormality has been previously reported in four patients, one of whom had ultrastructural abnormalities on liver biopsy. This paper describes a patient presenting with severe OHSS 16 days after ovulation had been induced. Liver function abnormality was apparent 11 days later, with a sustained rise in alkaline phosphatase and aspartate aminotransferase (AST) which lasted up to 2 months. A liver biopsy performed during the second month of her protracted hospital admission showed marked zonal fatty change (acinar zone 1) and associated inflammation, with mitochondrial crystalline inclusions and rough endoplasmic reticulum dilatation on electron microscopy. This report discusses the clinical features and possible aetiological factors.

Candida albicans--do mycelia matter?

Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA-2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth.

Diclofenac associated hepatitis.

Diclofenac is a widely used non-steroidal anti-inflammatory drug, being the most commonly prescribed of its kind in the world. This paper describes five cases of hepatitis with clinical features indicating a direct link with diclofenac. All the patients presented with an acute hepatitis, three being jaundiced. They gave a history of taking diclofenac up to the time of presentation, four of the five having started the drug within the previous 3 months. There were no other features in the histories to suggest alternative causes for the liver dysfunction. Liver function tests were grossly abnormal in all cases, showing a hepatitic picture. A liver biopsy was performed in 4 cases, and showed features of an acute hepatitis with inflammation and hepatocyte damage dominating. The liver dysfunction returned to normal on drug withdrawal in four of the five cases, with full recovery by 3 months. One patient developed steroid-responsive chronic active hepatitis. Hepatotoxicity associated with diclofenac is documented, but previously only a few isolated cases have been described. The occurrence of five cases in one gastroenterology unit over a 12-month period suggests that hepatitis associated with diclofenac may be commoner than previously supposed.

A study of patients with alcoholic liver disease by 31P nuclear magnetic resonance spectroscopy.

1. Patients with a history of alcohol abuse were studied by 31P n.m.r. spectroscopy of the liver in vivo, and the results were related to the pattern of disease assessed by standard biochemical and histological techniques. 2. The ratios of metabolites measured from the 31P n.m.r. spectra were abnormal in patients with alcoholic hepatitis but not in those with fatty change or cirrhosis in the absence of hepatitis. In particular, the levels of phosphomonoesters were raised, with respect either to Pi, or to adenosine 5'-triphosphate. The level of phosphomonoesters showed a significant positive correlation with the severity of alcoholic hepatitis, assessed by histology. 3. The ratio of Pi to adenosine 5'-triphosphate was used as a measure of the energy status of the hepatocytes, and was unchanged between patients and controls.

Effects of saturated sodium chloride solution on coccidial oocysts.

Using the ability to sporulate as a measure of viability, the effects of exposure of unsporulated oocysts of 10 species of coccidia of chickens, rabbits and cattle to saturated NaCl solution has been studied. Although appreciable deformation and collapse of the oocyst occurred after 1-2 days contact, the effect was reversible after washing free from salt and incubating. Some reduction in ability to sporulate following several days contact with saturated salt was noted in most species, although no effect was seen with Eimeria stiedai following 7 days exposure, Eimeria tenella was one of the more sensitive species studied. Culture titration experiments in chickens with E. tenella indicated that oocysts which had sporulated following prolonged exposure to salt were in no way inferior in virulence or ability to retain virulence on prolonged storage to oocysts prepared with minimal contact with salt. No evidence was obtained to contra-indicate the use of salt-flotation methods for the separation of oocysts from faeces.