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Biomedical subjects

C H Cameron

Publications and source records attributed to C H Cameron.

At least 19 recordsLinked to original sources

Characterisation of a cellular model of cardiomyopathy, in the rabbit, produced by chronic administration of the anthracycline, epirubicin.

The objective of this study was to assess the structural, mechanical and electrophysiological changes associated with chronic administration of epirubicin (Pharmorubicin), which is a cardiotoxic anthracycline antibiotic used in conventional cancer chemotherapy. New Zealand white rabbits (8 weeks) were treated with twice-weekly infusions of epirubicin (2 mg/kg) or saline for a period of 6 weeks, followed by a wash-out period of 2 weeks. Myocardial damage consistent with cardiomyopathy was observed in the epirubicin-treated animals; electron micrographs indicated myofibril loss together with separation of the intercalated disc and dilation of the sarcotubular system. Contractile function, as measured by mechanical shortening, action potentials and L-type Ca2+ currents were examined in ventricular cardiomyocytes, which were isolated by means of enzymatic dissociation using collagenase. There was an attenuation in the contractile response to isoprenaline in cardiomyocytes isolated from the hearts of epirubicin-treated rabbits compared to control rabbits. Cardiomyocytes isolated from epirubicin-treated rabbits had greater basal contractile amplitude (11.0+/-0.3 %dL, n=8) than control myocytes (8.2+/-0.3 %dL, n=9), but had similar maximum responses of 19.1+/-0.6 %dL, and 17.3+/-0.5 %dL, respectively, when stimulated with 1 microM isoprenaline. No differences were noted in the peak L-type Ca2+ current of myocytes isolated from the hearts of control and epirubicin-treated rabbits; however, in the latter, there was a prolongation of the action potential duration (396+/-25 ms) compared to that in controls (321+/-26 ms). These results demonstrate structural and mechanical alterations in ventricular cardiomyocytes which are compatable with a mild cardiomyopathy following chronic treatment with the anthracycline, epirubicin. The increase in basal contraction is likely to be due to more efficient coupling of electrical stimulation, and the depressed inotropic responsiveness following stimulation with isoprenaline indicates that there may be changes in cell membrane properties. Compared to control cardiomyocytes, cells isolated from the hearts of epirubicin-treated rabbits were more heterogeneous, with respect to cell dimensions, and had significantly different electromechanical properties.

Animals↗

Paraganglioma: an unusual tumour of the parathyroid gland.

A case of paraganglioma arising within a parathyroid gland is reported. The lesion was an incidental finding in a block dissection of neck performed for squamous carcinoma of the pharynx. A well-circumscribed lesion, exhibiting the characteristic pathological features of a paraganglioma, was embedded within the right inferior parathyroid gland. Due to its location, the chief histological differential diagnosis was an unusual variant of parathyroid adenoma. Immunohistochemistry and electron microscopy assisted in reaching a diagnosis. This, as far as we are aware, is the first reported case of a paraganglioma of the parathyroid gland.

Aged↗

Colitis complicating chronic granulomatous disease. A clinicopathological case report.

BACKGROUND: This report concerns a female patient now aged 24 years, diagnosed at the age of 7 years as suffering from chronic granulomatous disease. At age 20 she developed diarrhoea accompanied by rectal bleeding. Endoscopy showed extensive colitis. She failed to respond to medical treatment and underwent total colectomy two years later. AIMS: To discuss the histological changes in the colon in chronic granulomatous disease. RESULTS: There was extensive mucosal inflammation throughout colon and rectum resembling ulcerative colitis. In addition characteristic large pigmented macrophages were distributed in the basal mucosa and superficial submucosa. Similar cells accompanied by granulomata were present in mesenteric lymph nodes. CONCLUSIONS: Colitis is an unusual clinical manifestation of chronic granulomatous disease but the presence and characteristic distribution of such pigmented macrophages in colonic biopsy in children and young adults may suggest the diagnosis.

Adult↗

Desmin myopathy with cardiomyopathy.

We report a case of abnormal desmin accumulation within the muscle of a 30-year-old female with a 2-year history of cardiomyopathy and axial muscle weakness. Serum creatine kinase was normal. A quadriceps muscle biopsy revealed pink hyaline inclusions, which stained for acid phosphatase and with PAS and were present in both fibre types. Electron microscopy showed these inclusions to consist of aggregates of irregularly arranged 6- to 15-nm-diameter filaments enmeshed within a central core of dense granulo-amorphous material. In other areas, the granulo-amorphous material lay as irregular patches within the sarcoplasm, mainly at the level of the "Z" band causing disruption of the sarcomere. Immunoelectron microscopy using colloidal gold showed that the dense amorphous material reacted strongly with desmin antisera and could, therefore, represent a defective or phosphorylated form of the protein.

Adult↗

Dominantly inherited tubular aggregate myopathy.

We report an unusual familial myopathy characterized morphologically by the presence of large tubular aggregates in all fibre types. Two patients, a father and daughter, presented with slowly progressive proximal weakness, limitation of eye movement, and Achilles tendon contractures. Serum creatine kinase was 5-10 times normal. Light microscopy revealed type I fibre predominance. Basophilic accumulations, which stained intensely with the NADH-TR reaction, were present in both fibre types. Electron microscopy revealed that these consisted of tightly packed parallel tubular arrays. These varied somewhat in their ultrastructural appearance and were classified accordingly as type I, II, and III tubular structures. The tubular aggregates appear to be derived from the sarcoplasmic reticulum. This report further supports the evidence of a distinct clinico-pathological entity of genetic origin.

Adult↗

Hepatitis C virus: evidence for sexual transmission.

OBJECTIVE: To determined the prevalence of hepatitis C virus infection and associated risk factors in patients attending a genitourinary medicine clinic, as evidence for sexual transmission. DESIGN: Seroprevalence estimated by reactivity in an enzyme immunoassay for antibodies to C100 protein with supplementary testing with a recombinant immunoblot assay and an assay for hepatitis C virus RNA. SETTING: Outpatient genitourinary medicine clinic in central London. PATIENTS: The panel of 1046 serum samples was from 1074 consecutive patients attending the clinic during November and December 1987 and having blood taken for routine testing for syphilis. Before samples were anonymised demographic and risk factor information was extracted from the clinic notes. Samples had already been tested for antibody to HIV-I and antibody to hepatitis B core antigen. MAIN RESULTS: Significantly more homosexual subjects than heterosexual subjects were positive for hepatitis C antibody determined by enzyme immunoassay alone (19/275 (6.9%) v 8/771 (1.0%), odds ratio 7.14, p less than 0.0001) and also when reactive serum samples were also tested by recombinant immunoblot assay (6/270) (2.2%) v 3/770 (0.4%), odds ratio 5.88, p less than 0.02). There were also significant associations in patients positive for hepatitis C antibody with positivity for antibodies to HIV and to hepatitis B core antigen, lifetime number of sexually transmitted diseases (homosexual men only), and age (all groups combined). Most patients whose serum samples contained specific antibodies to hepatitis C virus were viraemic. CONCLUSIONS: The study provides strong evidence for the sexual transmission of hepatitis C virus. Assays derived from other gene products are desirable to investigate the specificity and sensitivity of the enzyme immunoassay for C100 antibody as a marker of hepatitis C virus infection.

Adolescent↗

Tartrate resistant acid phosphatase positive splenic lymphoma: a relatively benign condition occurring in a time-space cluster?

Conventional light and electron microscopic studies, together with cytochemical and immunocytochemical staining procedures, were carried out to ascertain whether the lymphomata of four elderly female patients living within 10 kilometers of each other, who presented within a short space of time with massive splenomegaly and varying cytopenia, belonged to any particular subgroup of lymphoma. In each case the lymphoma had a diffuse pattern and mature B cell phenotype. The malignant cells were of uniform cell type, slightly larger than admixed polymorphonuclear leucocytes, and showed minimal nuclear irregularity and positivity for tartrate resistant acid phosphatase (TRAP) staining. Their clinical and morphological features were compared with those of other lymphoproliferative disorders, but while sharing some features in common with each condition, this small group of patients seemed to have a unique combination of findings. The cytopenias of all four responded well after removal of the spleen and their disease has not been aggressive. It is concluded that these patients have a distinct subgroup of lymphoma, which it is important to recognise so that inappropriate use of aggressive cytotoxic drugs can be avoided.

Acid Phosphatase↗

Gastric paraganglioma: an immunohistological and ultrastructural case study.

This is a report of the immunohistochemical and ultrastructural features of a case of paraganglioma of the stomach in a 61-year-old woman who presented with melaena. The typical 'Zellballen' arrangement of epithelial cells with granular cytoplasm was present and the tumour was highly vascular. The polygonal epithelial cells stained strongly for neuron specific enolase and the intervening elongated sustentacular or support cells were positive for S100 protein and vimentin. Many dense core granules were present within the epithelial cells while the elongated support cells contained plentiful diffuse intermediate filaments. No hybrid cells or ganglion cells were present in the tumour. This is the sixth recorded case of gastric paraganglioma and the first to be studied in detail by immunostaining and electron microscopy.

Female↗

Spontaneous loss of HBeAg and the prevalence of HTLV-III/LAV infection in a cohort of homosexual hepatitis B virus carriers and the implications for antiviral therapy.

The future design of controlled trials of antiviral therapy which might include homosexual hepatitis B virus (HBV) carriers requires base-line data on the spontaneous rate of loss of HBeAg and the prevalence of human T-lymphotropic virus III (HTLV-III/LAV) infection. Fifty-one untreated HBsAg and HBeAg-positive homosexual HBV carriers were followed for a median HBeAg-positive time of 23.5 months (range 6-85.5). Ten lost HBeAg, giving an annual rate of spontaneous loss of HBeAg of 10%. This rate is considerably higher than the apparent rate in a previous report and has considerable implications for the interpretation of previous, and the design of future, controlled trials in this population. A rapid rise in the prevalence of anti-HTLV-III/LAV amongst HBV carriers was demonstrated from 1981 such that by 1984 over 60% of HBV carriers were anti-HTLV-III-positive. HBV-DNA polymerase levels were not significantly different in asymptomatic anti-HTLV-III/LAV-positive compared to anti-HTLV-III/LAV-negative HBV carriers. Nevertheless, since chronic HTLV-III/LAV infection in its later stages may potentiate HBV replication, it is a factor that will need to be considered together with many others in any trial stratification procedure.

Acquired Immunodeficiency Syndrome↗

Structure of the hepatitis B virus genome.

The extent and position of the single-stranded gap in DNA molecules from Dane particles isolated from two donors of the adw serotype were determined by molecular hybridization and electron microscopic methods. The results showed that in each preparation more than 99% of the circular molecules are of uniform length and contain both single- and double-stranded regions. They confirmed that one end of the short strand is fixed with respect to the single EcoRI site within the molecule and to the nick in the long strand, but they also showed that although the position of the other end is variable, there is a preferred minimum length of about 650 to 700 nucleotides for the single-stranded region.

DNA, Viral↗

Jejunal crypt cell abnormalities associated with methotrexate treatment in children with acute lymphoblastic leukaemia.

Jejunal mucosal crypts were examined in jejunal biopsies from eight children with acute lymphoblastic leukaemia who had recently received methotrexate treatment. By comparison with biopsies from children under investigation for suspected malabsorption crypt mitosis was significantly reduced and showed a negative correlation with the dose of methotrexate given prior to biopsy. The three major cell types were studied under light and transmission electron microscopy. Gut endocrine cells were unaffected by therapy and immature crypt enterocytes showed only patchy degenerative abnormalities. By contrast a number of Paneth cells showed striking structural alterations with vacuolar dilatation of the cytoplasm. The extent of this correlated with the time since methotrexate treatment rather than its dose and may have been a functional response rather than of a toxic nature.

Child↗

Contrasting patterns and frequency of antibodies to the surface, core, and e antigens of hepatitis B virus in blood donors and in homosexual patients.

An attempt was made to assess the significance of the relatively frequent low-titre positive reactions in radioimmunoassays for antibody to hepatitis B surface antigen. Serum specimens negative for surface antigen were assayed for antibodies to the surface, core, and e antigens of the Hepatitis B virus. Two populations were studied - one of low hepatitis B incidence (2000 blood donors) and one of high incidence (200 male patients attending a clinic for sexually transmitted diseases). The validity of some singly occurring low-titre anti-HBs and anti-HBc reactions is questioned, and the occurrence of positive reactions unrelated to previous hepatitis B infection inferred.

Antibodies, Viral↗