PubMed HealthSearch

Biomedical subjects

G Scott

Publications and source records attributed to G Scott.

At least 19 recordsLinked to original sources

Effect of cilofungin on phagocytosis and intracellular killing of Candida albicans by human neutrophils.

The effect of a beta glucan synthase inhibitor, cilofungin, amphotericin B and 5-fluorocytosine on opsonization, phagocytosis and intracellular killing of Candida albicans blastospores by glass-adherent human neutrophils was determined by microscopy and dye exclusion staining. Pretreatment of blastospores for 2, 4, 6 and 18 h with 1.25 mg/l cilofungin resulted in 24-28% of neutrophils ingesting compared to 24% with no drug present. There was no significant difference in the phagocytic index with increased incubation time. Percentage ingestion and phagocytic index values were not significantly different when blastospores were pretreated for 2 h in the presence of 3, 7, 15, 31 and 62 mg/l cilofungin. Comparable concentrations of amphotericin B and 5-fluorocytosine gave similar results. In the absence of cilofungin, intracellular killing after 2 h was 54%. In the presence of 1 and 10 mg/l cilofungin, 85-90% of intracellular blastospores were killed. Therapeutic levels of amphotericin B or 5-fluorocytosine did not enhance intracellular killing. These data demonstrate the potentiation of intracellular killing of Candida albicans by neutrophils in the presence of cilofungin.

Amphotericin B

A simple and rapid method for improving recording characteristics using multibarrelled micropipettes.

A method for the simple and rapid fabrication of multibarrelled micropipettes with improved signal-to-noise characteristics is described. The process of silicone coating the exterior of the multibarrel assembly was found to improve recording characteristics greatly and to reduce recording noise during the passage of ionophoretic current. This simple process of fabrication and silicone coating is completed within 15-20 min and is technically undemanding.

Action Potentials

Progressive multifocal leukoencephalopathy in HIV-1-infected children.

OBJECTIVE: To describe the clinical and pathologic features of two HIV-1-infected children with progressive multifocal leukoencephalopathy (PML). DESIGN: Case report. SETTING: University-affiliated, public-health trust hospital. METHODS: Two HIV-1-infected children with PML are described. A 13-year-old girl, presumed to be congenitally infected with HIV-1, presented with dysarthria and paresthesias of the tongue and chin that evolved rapidly to dementia, muteness and severe spastic quadriparesis. The other patient, a 10-year-old boy who developed HIV-1 infection from a blood transfusion at the age of 3 years, presented with a facial palsy with subsequent development of right hemiparesis and aphasia. RESULTS: Brain biopsy in the first child and autopsy in the second confirmed the diagnosis of PML. In both patients, the CD4 T-lymphocyte count was less than 100 x 10(6)l at the time of neurological presentation. CONCLUSION: Despite seroepidemiological studies suggesting that the majority of individuals are infected with JC virus during childhood, PML is rare in children with impaired cell-mediated immunity. Our patients illustrate that PML is among the neurological complications of HIV-1 infection in children.

Adolescent

Molecular mechanisms of human melanocyte attachment to fibronectin.

In this report we show that fetal and neonatal melanocyte attachment to fibronectin (FN) is inhibited by antibodies to the beta 1 integrin subunit, suggesting a role for these molecules in melanocyte attachment to FN. The VLA-5 integrin was shown to be the predominant receptor for fetal melanocyte attachment to FN, in contrast with neonatal melanocytes in which the very late antigen (VLA)-5, VLA-3, and alpha v integrins each contributed to melanocyte attachment to FN. Peptides containing the arginyl-glycyl-aspartyl-serine (RGDS) sequence inhibited fetal and neonatal melanocyte attachment to FN by a maximum of 48% and 85%, respectively. The almost complete inhibition of neonatal melanocyte attachment to FN by RGDS-containing peptides suggests that the central cell-binding domain of FN is the primary recognition site for neonatal cell attachment to FN. Fetal and neonatal melanocytes showed a concentration-dependent attachment to two proteolytically derived fragments of the FN molecule: a 75-kD fragment, which contains the central cell-binding domain, and 33/66-kD fragments of the FN molecule, which encompass the heparin-binding domains V and VI. Antibodies to the beta 1 subunit inhibited fetal and neonatal melanocyte attachment to the 33/66-kD fragments by a maximum of only 15% and 24%, respectively, suggesting that other, non-integrin, receptors are involved in melanocyte recognition of this portion of the FN molecule. We propose that human fetal and neonatal melanocytes attach to FN by different complements of receptors and ligand target sequences, and that these differences may direct melanocyte interactions with FN during development.

Antibodies

Continuous intratumoral infusion of methotrexate for recurrent glioblastoma: a pilot study.

Five patients with documented recurrences of glioblastoma multiforme were given continuous infusions of methotrexate delivered intratumorally using implantable catheters and subcutaneous refillable pumps. A continuous infusion of methotrexate (1 mg/d) was begun with concomitant oral administration of folinic acid. The methotrexate dose was increased every 2 weeks to 3, 10, 30, and, ultimately, 75 mg/d in two patients. Samples of serum and ventricular cerebrospinal fluid (CSF) were obtained to determine the levels of methotrexate and total bioactive folates, and brain tissue was obtained from two patients for determination of methotrexate concentration. The patients survived from 7 to 49 weeks after the implantation of the infusion device. Neither the clinical examination nor sequential radiological studies gave clear evidence of reduction in tumor size. Pneumonia developed in one patient, and mild hepatitis and increased seizure frequency in another. Methotrexate was stable in the delivery system over 12 days, and ventricular CSF reached steady-state levels by 5 days. Steady-state ventricular CSF levels of methotrexate were higher than serum levels in some patients, while the reverse was true in others. Levels of total bioactive folates in the CSF did not increase above the normal range. Methotrexate concentrations were highest at the center of the tumor, but measurable amounts of methotrexate were detectable in all areas of the brain. At autopsy in four patients, variable liquefactive necrosis of the brain tumors was seen, and viable tumor was found at the periphery of the tumor bed. These preliminary results suggest that it is technically feasible to infuse methotrexate into brain tumor cavities, and show that little central nervous system or systemic toxicity was encountered in five patients. Better delineation of the safety and efficacy of this therapeutic approach will require further clinical trials.

Brain Chemistry

Localization of basic fibroblast growth factor mRNA in melanocytic lesions by in situ hybridization.

Basic fibroblast growth factor (bFGF) is a mitogen for normal human melanocytes and keratinocytes in culture. Experiments in vitro suggest that keratinocytes supply bFGF to melanocytes through a paracrine mechanism and that the aberrant expression of bFGF in melanomas confers growth independence from bFGF-producing cells. To determine whether bFGF is expressed in vivo, we examined a series of benign and malignant melanocytic lesions in situ using bFGF riboprobes on tissue sections, and correlated bFGF expression with histologic phenotype. Seventeen melanocytic neoplasms were studied, including four common acquired nevi, four dysplastic nevi, four primary malignant melanomas, and five metastatic melanomas. Nevic cells in benign intradermal nevi showed low signal intensity (1+), whereas compound and dysplastic nevi showed 2+ to 3+ expression in the junctional nevic cell population and 1+ expression in the dermal nevic cell population. Melanocytes in primary melanomas had intermediate (2+) and those in metastatic melanomas had low (1+) levels of bFGF gene transcripts. Fibroblasts expressed high levels (3+) and epidermal and adnexal keratinocytes moderate (2+) levels of bFGF in all cases studied. Basic FGF expression in endothelial cells, known to produce and respond to this growth factor in vitro, was lower than that in the fibroblast and keratinocyte cell population and, in 10 of 17 cases, no bFGF mRNA was detectable. This study shows that bFGF is expressed in nevomelanocytes in vivo in all melanocytic lesions studied and thus cannot be used as a marker for transformation. The presence of bFGF gene transcripts in the various dermal cell types and in keratinocytes suggests that it may act as an autocrine and paracrine growth factor in regulating cellular proliferation in the skin.

Fibroblast Growth Factor 2

Dihydroergotamine suppositories in a headache clinic.

Dihydroergotamine (DHE) is available in the United States for parenteral use. We report a preliminary trial of DHE suppositories in an outpatient headache clinic setting. Dihydroergotamine suppositories may be appropriate for patients with catamenial migraine and classic migraine in particular.

Dihydroergotamine

Modification of an aerosol mask to provide high concentrations of oxygen in the inspired air. Comparison to a nonrebreathing mask.

With a few simple modifications, an aerosol mask was adapted to deliver high concentrations of oxygen. We compared the delivery of high concentrations of oxygen by this modified aerosol mask (MAM) with that of a nonrebreathing mask (NRM) in five normal volunteers and six patients with respiratory failure. Besides improved oxygenation, the MAM also permitted the following: humidification of the inspired oxygen, nebulization of bronchodilators, oropharyngeal suctioning, and performance of fiberoptic bronchoscopy. In lieu of intubation and mechanical ventilation, MAM may be a better alternative to a NRM for maintaining adequate oxygenation until the clinical situation improves.

Adult

The use of interferon-alpha in virus infections.

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.

HIV Infections

Roentgenographic assessment in hallux valgus.

Which simple roentgenographic angle should be used to assess medial (varus) deviation of the first metatarsal in cases of hallux valgus has been a topic of debate. Measurements were made from roentgenograms of 100 symptomatic feet in women with hallux valgus. These were compared with similar measurements obtained from symptomatic normal feet of women of a similar age distribution. The hallux valgus angle was associated with medial deviation of the first metatarsal measured by all three of the parameters defined and tested, i.e., the intermetatarsal, metatarsus primus varus, and metatarsus omnis varus angles. Of these, the best measure was the intermetatarsal angle, which in the hallux valgus feet differed significantly from controls more than the other measurements. No evidence was found to support any concept of second metatarsal deviation from normal.

Adolescent

Skin necrosis associated with acquired protein C deficiency in patients with renal failure and calciphylaxis.

PURPOSE: To determine if the natural anticoagulant protein C plays a role in the pathogenesis of systemic calciphylaxis, a syndrome characterized by extensive vascular and soft tissue calcification and skin necrosis, which is similar to that seen in warfarin-induced skin necrosis. PATIENTS AND METHODS: The study population included five patients with end-stage renal disease and systemic calciphylaxis undergoing hemodialysis, 12 patients without evidence of calciphylaxis undergoing dialysis, eight patients with nephrotic syndrome, and eight normal healthy volunteers. Protein C antigen levels were measured by rocket immunoelectrophoresis, and functional activity was quantitated by a chromogenic assay and an anticoagulant assay utilizing the venom of Agkistrodon contortrix. RESULTS: Skin biopsy specimens of involved areas in three patients showed thrombotic occlusion of venules identical to that seen in warfarin-induced skin necrosis. Protein C antigen levels were normal in all groups. However, protein C activity was significantly reduced as measured by chromogenic (p less than 0.01) or anticoagulant assays (p less than 0.01) in patients with calciphylaxis compared with the other three groups. CONCLUSION: These findings suggest that hypercoagulability due to functional protein C deficiency may contribute to thrombosis, resulting in skin necrosis and digital gangrene in systemic calciphylaxis.

Adult

Sequential autonomic function tests in HIV infection.

Cardiovascular autonomic function tests were carried out on 22 men at varying stages of HIV infection. Thirteen were asymptomatic, seven had persistent generalized lymphadenopathy, and two had Kaposi's sarcoma. Pupil cycle times were also measured. Except for one subject with definite autonomic abnormalities, all the rest had almost normal test results. There were no correlations between individual tests of immune function and the autonomic test results. The tests were repeated 9-18 months later in 12 men, four of whom were taking zidovudine at that time. Although there was evidence of progression of HIV-associated immune dysfunction, there was no significant deterioration in autonomic function. In the single patient with abnormal autonomic function, these changes appeared to reverse on treatment with zidovudine.

Adult

Cervical myelopathy in C.P.P.D. deposition disease.

Cervical Myelopathy is a rare manifestation of calcium pyrophosphate dihydrate (C.P.P.D.) deposition disease. A case is presented where radiographically noncalcified extradural masses containing C.P.P.D. crystals were present at the C7 level, producing cord compression and neurological symptoms. These masses are thought to represent para-articular deposits related to the adjacent facet joints.

Aged