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Biomedical subjects

G M Scott

Publications and source records attributed to G M Scott.

At least 55 records · Page 3Linked to original sources

New drug treatments for HIV infection and AIDS. A review following the Seventh International Conference on AIDS, Florence 16-21 June 1991.

1. OBJECTIVE--To evaluate the status of clinical development of zidovudine and new drugs for the treatment of Human Immunodeficiency Virus (HIV) infections. 2. METHOD--A critical review of the clinical trial reports and assessment of the design and methodology of the therapeutic trials. Evaluation of the drugs being tested and of the specific difficulties in testing drugs in AIDS. 3. CONCLUSIONS--Drugs are being tested in a unique climate of public opinion characterised by (1) fast track criteria for regulatory approval (2) parallel track (compassionate release) of new drugs before adequate determination of safety and efficacy (3) resistance to the use of placebos in controlled trials.

Acquired Immunodeficiency Syndrome↗

Predicting deterioration of treated tuberculosis by corticosteroid reserve and C-reactive protein.

Eighteen patients with recently diagnosed pulmonary tuberculosis were studied for factors which could predict, at the outset, reactions to treatment. Abnormally low corticosteroid responses to tetracosactrin were seen in some but not all of the patients who deteriorated while on treatment. Those who deteriorated transiently or died had pre-treatment C-reactive protein (CRP) concentrations above 20 mg/l, which then persisted. As previously observed, those who responded unfavourably were older, had extensive disease and presented with hypoalbuminaemia and hyponatraemia.

Adrenal Cortex Hormones↗

Assessment of the Axicare human milk pasteuriser (CM80).

The performance of the Axicare human milk pasteurizer was evaluated under different load conditions. The design criteria for pasteurisation specified that milk should be held at 63 degrees C for 30 min. The holding time at this temperature was insufficient if bottles of milk frozen at -20 degrees C were placed into the machine as directed, after the water-bath preheating phase. However, if the machine was loaded with frozen bottles before the whole cycle was commenced, adequate thawing and warming to holding temperature was achieved in sufficient time for satisfactory pasteurization. The pasteurizer gave consistent and adequate temperature and time conditions. The seals on three types of bottles tested tended to leak during the pasteurization cycle but no method of avoiding this problem was established.

Evaluation Studies as Topic↗

Immune status in tuberculosis and response to treatment.

Thirty hospitalized patients with newly diagnosed tuberculosis were studied prospectively with a range of in vitro and in vivo tests of immune function. Responses were compared with those of healthy controls matched for age, sex, ethnic group and diet. A series of metabolic and immunologic abnormalities was found, including evidence of undernutrition, anaemia, neutrophil leucocytosis, monocytosis, lymphopenia, hyperglobulinaemia and raised erythrocyte sedimentation rate. Some patients had accelerated, others diminished, cutaneous tuberculin hypersensitivity, and some had diminished mononuclear cell proliferative and lymphokine responses to tuberculin (purified protein derivative, PPD). The patients were not uniform in their responsiveness, but could be arranged within a spectrum which showed a relationship to crude bacillary excretion and response to treatment. 27% of patients were characterized by hypersensitivity, with normal in vitro cellular responses and skin tests to PPD, scanty bacillary excretion and rapid bacteriologic sputum conversion to negative cultures with treatment. In contrast, 30% of patients were relatively anergic with negative skin tests, reduced or absent in vitro cellular reactivity to PPD, moderate or heavy bacillary excretion and later (greater than 4 weeks) bacteriologic sputum conversion. The remainder of the patients fell between these two groups. There were no correlations between cellular immunity on the one hand, and radiological extent of disease, levels of serum immunoglobulins, peripheral white cell counts or ESR on the other. In those patients followed throughout treatment, all the abnormalities with the exceptions of arm muscle circumference and serum albumin, reverted to the normal ranges established in the control group.

Adult↗

Cross-infection between animals and man: possible feline transmission of Staphylococcus aureus infection in humans?

An outbreak of epidemic methicillin-resistant Staphylococcus aureus occurred on a rehabilitation geriatric ward. Intensive screening of patients and staff revealed an unusually high carriage rate in the nursing staff (38%), thought to be related to a ward cat which was heavily colonized from the environment. Infection control measures and removal of the cat led to rapid resolution of the outbreak.

Aged↗

Herpes simplex virus and facial palsy.

An 8-year-old boy developed acute herpes simplex virus stomatitis followed by transient facial palsy. The possible relationship between this virus and Bell's palsy is discussed.

Child↗

Acute respiratory distress related to chemotherapy of advanced pulmonary tuberculosis: a study of two cases and review of the literature.

Two patients with non-miliary pulmonary tuberculosis developed a syndrome resembling adult respiratory distress following initiation of drug treatment. They were studied clinically and with a representative range of in vitro and in vivo tests of immune function. Both were alcoholic, malnourished and presented with radiologically widespread, smear-positive disease and lymphocytopenia. One had cutaneous anergy in vivo and profound reduction on mononuclear cell proliferative and interferon responses to tuberculoprotein (PPD) in vitro; the other patient, who died two weeks after starting treatment, had relatively normal values for these measures of cell-mediated immunity. In both cases there was a progressive increase during treatment, in peripheral blood lymphocyte counts, skin reactions and in vitro cellular responses to PPD, and a sudden rise in ESR at the time of their deterioration. We propose that the reactions may represent local manifestations of heightened delayed hypersensitivity, mounted by increasing numbers of 'resuscitated' lymphocytes against immunogenic cell wall substances released from dying tubercle bacilli in patients whose level of cellular immunity is being enhanced as a result of chemotherapy. The likelihood of an acute respiratory reaction during treatment may therefore depend on the bacillary load, the extent of lung disease present, and its severity may be related to the pre-treatment immune status of the patient.

Adult↗

Characterization of the actin-binding site on the alkali light chain of myosin.

1H-NMR experiments on myosin subfragment-1 (S1) isoenzymes, containing either the A1 or the A2 alkali light chains (S1(A1) or S1(A2)), have previously suggested the 41-residue proline, alanine and lysine-rich N-terminal extension of A1 to constitute a mobile 'domain' in solution. This segment of the molecule is immobilised in the presence of actin (Prince et al. (1981) Eur. J. Biochem. 121, 213-219). We now establish that the A1 light chain interacts with actin directly, and furthermore, that the binding site appears to be restricted to the terminal 41 residues. This observation carries important consequences for both the structure of the actomyosin complex and the role of myosin isoenzymes. Using the proteinase, thrombin, a technique has been developed in which the A1 light chain is cleaved, releasing the N-terminal 'tail' from an A2-like fragment. The method is shown to be widely applicable to light chains from a variety of sources. The isolated N-terminal fragments from rabbit skeletal and bovine cardiac muscle have been shown to interact directly with actin by a combination of affinity chromatography and 1H-NMR experiments. The 1H-NMR results are similar to those obtained earlier with S1 (ibid) and suggest the terminal alpha-N-trimethylalanine residue (Henry et al. (1982) FEBS Lett. 144, 11-15) to participate in the interaction.

Actins↗

How useful are serum and CSF interferon levels as a rapid diagnostic aid in virus infections?

Specimens from a total of 162 patients were studied prospectively using a rapid nucleic acid synthesis inhibition assay and a plaque-reduction assay to detect interferon levels in serum and cerebrospinal fluid. The specificity, consistency, and diagnostic applications of the rapid assay were evaluated by intensively investigating each patient for possible viral illness. Forty-one percent of patients with proven acute virus infections (excluding those with acute hepatitis and infectious mononucleosis) had unequivocal detectable interferon in serum or cerebrospinal fluid, compared with only two patients with bacterial infections (7%) who had equivocal interferon in the serum. Retrospective analysis showed the test to have high specificity for virus infections, but in patients with clinical syndromes of uncertain aetiology the test was not a particularly sensitive indicator of the presence of subsequently detected virus. The presence of interferon was not related to the time during the illness at which the sample was taken, nor to the numbers of lymphocytes in the cerebrospinal fluid, nor to the patients' general symptoms.

Biological Assay↗

Tolerance of one-month intranasal interferon.

Under double-blind conditions, groups of volunteers (68 in total) were allocated at random to take intranasal solutions of placebo or one of three doses of highly purified leucocyte interferon by intranasal spray twice a day for 28 days. The highest dose would have been expected to protect against experimental colds. Treatment was discontinued because of upper respiratory symptoms as often in each of the interferon groups as in the placebo group. However, it was possible to distinguish clinically between "colds" on placebo and low-dose interferon and "reactions to treatment" on high-dose interferon. The features of the reactions to treatment were a protracted build-up of local symptoms and minor epistaxis. None of the volunteers on the high-dose interferon were thought to have a definite cold, but viruses were isolated from four out of six volunteers on low-dose interferon who had definite colds. Previous experiments had also shown this dose to be insufficient to protect against experimental rhinovirus challenge. The dose of interferon that appeared to protect against virus infection caused significant unwanted effects. It is essential to find interferon preparations with less inflammatory activity before interferon can be considered for use as a long-term prophylactic against the common cold.

Administration, Intranasal↗

Natural killer cell activity in tuberculosis.

Natural killer (NK) cell activity was studied in 27 patients with active tuberculosis and 27 healthy controls matched for age, sex, ethnic origin and diet. Spontaneous and interferon (IFN)-augmented NK cytotoxicity against K562 target cells were measured, using a 4-hour 51Cr-release assay. There were no differences between the patients and their matched controls in mean spontaneous and IFN-augmented cytotoxicity before and during antituberculosis chemotherapy. However, one malnourished alcoholic patient with extensive non-reactive multibacillary disease had depressed NK cell activity which was not significantly enhanced by in vitro pretreatment with leucocyte IFN. We conclude that the NK system is not of prime importance in host defence against human tuberculosis, although advanced disease may be associated with deficient NK activity, as part of generalized anergy.

Adolescent↗

Viral keratitis.

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Adenoviridae Infections↗

Measurement of interferon from in vitro stimulated lymphocytes by bioassay and monoclonal antibody-based immunoassay.

Peripheral blood mononuclear cells (PBMC) derived from healthy individuals were stimulated with u.v.-inactivated Newcastle disease virus and the cell supernatants were assayed for both antiviral activity and alpha interferon (IFN-alpha) immunoreactivity. IFN-alpha concentrations determined by two immunoradiometric assays (IRMAs) based on monoclonal antibodies that recognize different IFN-alpha subtypes correlated well together (r = 0.96) and with interferon concentrations determined by the two bioassays (r = 0.82 to 0.89), but the agreement between the results of the two bioassays was not as close (r = 0.79). As judged by the agreement between determinations on duplicate inductions of the same PBMC, the IRMAs were considerably more precise than the bioassays. Despite the use of a common IFN standard there were marked differences in the absolute titres of IFN determined by the IRMAs and bioassays, highlighting the difficulties in standardizing assays for IFN-alpha. The IRMA results suggest that there are no major differences in the spectrum of IFN-alpha subtypes produced by healthy individuals under conditions of viral stimulation.

Animals↗

Deficient immune interferon production in tuberculosis.

Production of interferon (IFN)-alpha and -gamma by peripheral blood mononuclear cells (PBMC) were studied in 28 patients with active tuberculosis and 28 healthy control subjects matched for age, sex, ethnic origin and diet. No significant differences were found between patients and matched controls in mean titres of IFN-alpha induced by Newcastle disease virus, IFN-gamma induced by staphylococcal enterotoxin A with tetrahydrophorbyl acetate, and IFN-gamma induced by purified protein derivative (PPD). However, a subset of nine out of 25 tuberculosis patients tested produced low titres (less than 100 u/ml) of IFN-gamma in response to PBMC stimulation with PPD. In comparison to other patients, this group was characterized by lower IFN-alpha and IFN-gamma responses to virus and mitogens respectively, relative anergy to tuberculin skin testing, depressed in vitro PBMC proliferative responses to PPD, and neutrophil leucocytosis. In all nine patients effective chemotherapy restored cutaneous reactivity, PBMC proliferative responses, neutrophil counts and IFN-alpha responses to virus by 6 months, and also IFN-gamma responses to PPD in one patient re-tested.

Adolescent↗