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Biomedical subjects

M Longson

Publications and source records attributed to M Longson.

At least 19 recordsLinked to original sources

Donor seropositivity and prednisolone therapy as risk factors for cytomegalovirus infection and disease in cyclosporin-treated renal allograft recipients.

We attempted to assess the importance of blood transfusion, donor seropositivity, and prednisolone therapy as risk factors for cytomegalovirus infection in cyclosporin-treated renal allograft recipients. Primary infection was diagnosed in 27 of 86 patients (31 per cent) and recurrent infection in 27 of 79 patients (34 per cent). Receipt of banked blood from unselected donors after transplantation did not increase the incidence of primary infection in the few transfused patients. Kidney donor seropositivity and maintenance prednisolone in addition to cyclosporin were associated with increases in the incidence of primary or recurrent infection, respectively. Cytomegalovirus infection was clinically mild. Presumed bacterial pneumonias occurred in three patients with recurrent cytomegalovirus infection. The absence of severe cytomegalovirus disease probably reflected the minimal use of prednisolone. Matching of seronegative donors with seronegative recipients seemed unjustifiable in cyclosporin-treated renal transplant patients.

Adult

Antiphospholipid antibodies and Mycoplasma pneumoniae infection.

Anticardiolipin antibody levels were measured in 57 patients with Mycoplasma pneumoniae infection and 21 patients with other infections. Significantly more patients in the mycoplasma group had increased IgM and IgG anticardiolipin. Within the mycoplasma group significantly higher titres were found in patients with severe infection (assessed by need for hospital admission) and in patients with cold agglutinins. A tendency for particularly high titres to occur in patients with extra-pulmonary complications was identified.

Adolescent

Altered in vitro uptake of the radiolabelled antiviral imaging "probe" E-5-(2-125iodovinyl)-2'-deoxyuridine following administration of acyclovir.

Current developments in the use of radiolabelled antiviral drugs as specific "probes" for virus-infected cells in vivo may allow the specific neuroradiological diagnosis of herpes encephalitis. As "blind therapy" with the antiviral drug acyclovir may precede specific neuroradiological diagnosis, the aim of the present study was to investigate whether or not acyclovir interferes with the uptake of the radioprobe E-5-(2-125Iodovinyl)-2'-deoxyuridine (rIVDU) by virus-infected cells in vitro. Acyclovir treatment (0.1 to 10 micrograms/ml) was shown to increase initial radioprobe uptake by virus-infected cells. However, with continued incubation in the presence of acyclovir, intracellular radioactivity decreased to a level not significantly different from that associated with noninfected cells. A mechanism to explain these results is proposed. It was concluded that concurrent acyclovir therapy could interfere with neuroradiological diagnosis using rIVDU, although this may not occur with all the candidate radioprobes currently under investigation.

Acyclovir

Specific neuro-radiological diagnosis of herpes encephalitis in an animal model.

The potential of utilizing a radio-labelled derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) for the specific, non-invasive, in vivo diagnosis of Herpes simplex virus encephalitis (HSVE) was investigated in a rat model of the disease. Following pharmacological disruption of the blood brain barrier radiolabelled IVDU was administered by intra-carotid injection. Brain radioactivity was compared between control and infected animals via gamma camera scintigraphy. After clearance of non-metabolized drug, markedly higher levels of activity were found in infected brain. Post-mortem studies of cryostat sections of brain examined by autoradiography and immunochemical staining showed the radioactivity selectively accumulated in areas of virus infection. These results indicate that radio-labelled derivatives of antiviral drugs may allow the specific neuro-radiological diagnosis of HSVE.

Animals

Human papillomavirus (HPV) genotypes associated with laryngeal papilloma.

Biopsy specimens from 14 patients treated for laryngeal papillomatosis were tested for the presence of human papillomavirus (HPV) genome by the technique of DNA-DNA hybridisation. According to the age of initial presentation, cases were subdivided into juvenile (less than 16 years) and adult onset (older than 16 years) groups. Histological investigation confirmed that it was impossible to distinguish the groups on this basis. Molecular virology using both dot blot and Southern transfer techniques showed that 10 cases carried the HPV type 6 genome, three cases HPV type 11, and in one case no HPV DNA was detected. All six adult onset cases carried HPV 6 sequences while the juvenile onset group comprised four HPV 6 and three HPV 11 cases. In the juvenile onset group more females were affected; in the adult onset group more males were affected. Two of the patients shown to have HPV type 11 sequences in their biopsy material were the most resistant to treatment. One of the adult onset cases subsequently developed a squamous cell carcinoma of the larynx in which HPV 6 DNA was detected. As far as we know this is first time that HPV-DNA has been confirmed in laryngeal papilloma undergoing malignant change.

Adult

Penetration of the blood-brain barrier by the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine in a rat model of herpes encephalitis.

The blood-brain barrier penetration of a radiohalogenated (125I) derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) was investigated in a rat model of herpes encephalitis. CNS delivery was assessed by external gamma camera scintigraphic imaging in vivo, a technique which may have general application in evaluating brain specific delivery of drugs, and by autoradiography of cryostat sections of rat brain. Radiohalogenated IVDU was found to be almost totally excluded from the CNS. These findings may be explained in terms of the poor lipid solubility of IVDU (in vitro oil/aqueous salt solution partition coefficient 0.012). Since IVDU appears in CSF after carotid artery administration, our results stress the necessity, in the design of compounds for the treatment of CNS infections, of distinguishing blood-brain, blood-CSF, and CSF-brain drug barriers. The significance of our data both in relation to the development of neuro-radiological diagnosis and antiviral chemotherapy of CNS infection is discussed.

Animals

A rat model of herpes encephalitis with special reference to its potential for the development of diagnostic brain imaging.

A rat model of herpes encephalitis using intraocular inoculation of herpes simplex virus strain SC16 was investigated. Virus distribution in the brain was examined by virus isolation and immunocytochemical staining using immuno-gold silver and peroxidase-anti-peroxidase. At 5 days post-infection virus was found in the thalamus, hypothalamus, septum, colliculus, geniculate bodies, the pons, trapezoidium and medulla oblongata, but less frequently, in the cerebellum and occipital lobes. Possible routes of spread of virus and the potential of this model in neuro-radiological scanning procedures are discussed.

Animals

Chronic Q fever endocarditis with massive splenomegaly in childhood.

Two children with congenital heart disease developed persistent fever, anemia, and hepatosplenomegaly. Both were shown to have intracardiac vegetations and evidence of infection with Coxiella burnetti. Thus, the same clinical manifestations of Q fever may develop in both children and adults.

Adolescent

Effect of selective vaccination on rubella susceptibility and infection in pregnancy.

The effect of school and adult vaccination on susceptibility to rubella in women of childbearing age was assessed in the Manchester area, where the population attending antenatal clinics is over 40 000 a year. Between 1979 and 1984 the proportion susceptible fell from 6.4% to 2.7%. In 1984, 4.2% of nulliparous women were susceptible compared with 1.4% of women in their second or subsequent pregnancy. Eighty five per cent of pregnant women screened and found to be non-immune were vaccinated post partum before leaving hospital. Requests for prevaccination screening of non-pregnant women increased in response to a national campaign and at the time of local outbreaks of rubella but only two thirds of those found to be nonimmune were subsequently vaccinated. During 1983 and 1984 infection was confirmed in 57 pregnant women--2% of those non-immune. Selective vaccination has reduced susceptibility to rubella in the childbearing population, but it is suggested that mass vaccination of children of both sexes should be added to the existing policy to control circulation of wild rubella virus and reduce the risk of infection to pregnant women who remain susceptible.

Adolescent

Herpes simplex infections in atopic eczema.

One hundred and seventy nine children with atopic eczema were studied prospectively for two and three quarter years; the mean period of observation being 18 months. Ten children had initial infections with herpes simplex. Four children, very ill with a persistently high fever despite intravenous antibiotics and rectal aspirin, continued to produce vesicles and were given intravenous acyclovir. There were 11 recurrences among five patients. In two patients the recurrences were as severe as the initial lesions, and one of these children had IgG2 deficiency. Use of topical corticosteroids preceded the episode of herpes in only three of the 21 episodes. Symptomatic herpes simplex infections are common in children with atopic eczema, and are suggested by the presence of vesicles or by infected eczema which does not respond to antibiotic treatment. Virological investigations are simple and rapid: electron microscopy takes minutes, and cultures are often positive within 24 hours.

Child

Persistence in herpes simplex virus infections.

Diseases of man caused by the virus of herpes simplex fall into two broad categories. The primary disease occurs only once in any individual's life and is caused by transmission of virus from an already infected human. Thereafter, the individual may be subject to recurrent herpetic disease, the manifestations of which are different from the primary disease. Recurrent disease varies in severity from trivial, to incapacitating and frankly lethal (as in diseases resulting from the virus's neurotropic and oncogenic properties). The source of the virus in recurrent herpetic disease has never been conclusively resolved, but is almost certainly endogenous to the patient. Theories, case reports and experiments exist to show that endogenous virus may, in periods of clinical quiescence, be latent (or persistent) at the site of the recurrent lesions itself, or more remotely in nerve tissues related to the site of recurrence.

Animals

Herpes encephalitis.

Four cases of herpes encephalitis treated with dexamethasone and cytarabine. Cases were all verified by brain biopsy and immunofluorescent techniques. Attention is called to the need for early diagnosis, but the difficulty of deciding when to perform brain biopsy is discussed. Early treatment with effective drugs is necessary to prevent permanent brain damage.

Adolescent

Influenzavirus A2 infections presenting with febril convulsions and gastrointestinal symptoms in young children.

We present the clinical features of Influenzavirus A2 infection in 75 young children admitted to a children's hospital. The most common presenting features were febrile convulsions. vomiting, coughing, diarrhea, and anorexia. At any age, the illness may present with respiratory tract symptoms and signs but in young babies gastroinestinal symptoms are often the presenting complaint. Children aged one to three years often present with febrile convulsions. Only in older children does the adult pattern begin to emerge. Evidence is put forward to suggest that encephalitis in association with influenza can be due to direct invasion of the central nervous system by the virus.

Adolescent

Chronic Q fever.

Sixteen cases of chronic Q fever are described. In eight there was a history of exposure to infection from farms or farm products. All had valvular heart disease, involving the mitral valve in nine and the aortic valve in seven. Infection occurred on a prosthetic valve in two patients. Arterial embolism was common. Venous thrombosis occured in three patients, and pulmonary embolism occurred in three other patients. Complement fixing antibodies to phase 1 antigen were found in a titre of 1:200 or greater in all except two patients. In one of these post-mortem examination revealed rickettsial bodies in mitral valve vegetations, and in the other Coxiella burneti was isolated from heart valve tissue. The majority presented with infective endocarditis but two presented primarily with liver disease. All patients had evidence of liver involvement and in one this led to death from cirrhosis. Abnormal tests of liver function, particularly hyperglobulinaemia, raised alkaline phsophatase and abnormal bromsulphthalein retention were found in all patients. Hepatic histology was abnormal in all eight patients in whom it was studied. The commonest features were mononuclear cell infiltration of the portal tracts and prominence of the sinusoidal Kupffer cells. Patchy focal necrosis of parenchymal cells, granulomata, fatty change, and eosinophilia of the sinusoidal walls were also noted in several patients and cirrhosis developed in one. Six patients had a purpuric rash, and in 12 there was thrombocytopenia. It is suggested that the presence of hepatomegaly and liver involvement and thrombocytopenia may help to differentiate Q fever endocarditis from bacterial endocarditis. Raised serum IgM and IgA levels occured frequently, but with only a moderate dominance of IgM. Sheep cell agglutination and latex fixation tests for rheumatoid factor were occasionally positive. Several features of the disease suggest the possibility that immune-complex mechanisms may play a role in chronic Q fever. Treatment was with prolonged courses of tetracycline usually combined with lincomycin. Seven patients underwent valve replacement surgery for haemodynamic reasons. Five patients died; two from heart failure, one from cirrhosis, one seven days after valve replacement and one from intraperitoneal haemorrhage following percutaneous liver biopsy. Three patients have survived for more than five years, and another six for more than three and a half years after diagnosis. Of these nine patients, three received medical therapy alone and six required valve replacement as well. Antibiotics have been discontinued in four patients who have had valve surgery and three others. Six patients had received antibiotics for continuous periods varying from 29-62 months. In the period after stopping therapy varying from 15-21 months, no relapse has occured. A seventh patient, who had received antibiotics for four months prior to valve replacement, has survived 43 months after the withdrawal of antibiotics...

Adult