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Biomedical subjects

S Gregory

Publications and source records attributed to S Gregory.

At least 19 recordsLinked to original sources

Cytokines in the vitreous of patients with proliferative diabetic retinopathy.

Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy.

Adult

The generation of ordered sets of cosmid DNA clones from human chromosome region 11p.

We describe progress in a continuing project aimed at the generation of an overlapping cosmid DNA clone map of the short arm of human chromosome 11. The automated procedures used to prepare DNA samples and the computerized data collection and recording systems are described. We also demonstrate the use of the clones as reagents for the rapid isolation of genomic DNAs containing smaller probed regions. We have isolated approximately 4700 human cosmid DNA clones from mouse/human hybrid cell lines that contain predominantly human chromosomal region 11p. Of the DNA in the cell lines, 60% is derived from this chromosomal region, and the remaining 40% is derived from regions of chromosomes 3, 19, and 20. A total of 4159 clones have been fingerprinted to identify potential overlaps, and we have developed 535 sets ("contigs"). Using random modeling, it is estimated that 65% of 11p must be contained in the analyzed cosmids. The database of clones has been used to identify single or overlapping clones from noncosmid DNA probes. Examples are presented. It is proposed that cosmid reference filters be distributed to requesting laboratories.

Chromosome Mapping

Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis.

Interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF alpha), and IL-6 are cytokines which mediate cellular responses during immune activation and inflammation. In multiple sclerosis (MS) they might be responsible for T-cell activation (IL-1 beta), for demyelination (TNF alpha), and for immunoglobulin (Ig) synthesis (IL-6) within the central nervous system. We studied IL-1 beta, TNF alpha, and IL-6 levels in the cerebrospinal fluid (CSF) of 34 patients with MS, 43 patients with non-inflammatory neurological diseases (NIND), and 19 patients with inflammatory neurological diseases (IND). IL-6 was found in the CSF of 29% of MS, 7% of NIND, and 47% of IND patients. TNF alpha was detected in the CSF of 23% of MS, 7% of NIND, and 29% of IND. CSF IL-6 and TNF alpha levels were significantly higher in MS and IND than in NIND. IL-1 beta was rarely detected in the CSF of any group. At least one cytokine was detected in 52% of MS CSF, 11% of NIND CSF, and 64% of IND CSF. In MS patients, no relationship was observed between the incidence or the amount of intrathecal IgG synthesis or oligoclonal bands and the presence of any cytokine. We also evaluated cytokine levels in paired sera from 11 MS and 13 NIND patients. Low levels of IL-6 were detected in most sera from MS and NIND patients. TNF alpha was detected in only two MS sera, and IL-1 beta was undetectable in any sample. Our results indicate that increased CSF levels of the cytokines IL-6 and TNF alpha occur frequently in MS and IND, but there is no obvious relationship to intrathecal Ig synthesis.

Adult

Serial studies of evoked potentials and circulating lymphocyte subsets for multiple sclerosis: attempts to monitor progress.

A concurrent change in evoked potential measurements and quantitation of circulating T-suppressor (CD8) lymphocyte subpopulations might indicate increased subclinical disease activity. Eight untreated patients with clinically definite multiple sclerosis were monitored monthly for changes in the numbers of cells positive for CD8 markers, and hence in the ratio of CD4: CD8 positive cells. Such changes were found not to be associated with changes in evoked potentials or clinical status.

Adult

Adding a microcomputer bar-code network to a minicomputer-based radiology information system.

A bar-code terminal network under software control of a microcomputer was added to the minicomputer-based radiology information system at the Medical College of Georgia in Augusta. The bar-code network was specifically installed to address the inherent inaccuracies occurring when procedure information was entered at the time of registration before procedures were actually performed. Technologists now enter procedure data into bar-code terminals after procedures are performed, substantially reducing database errors. This approach allowed us to take advantage of a microcomputer product without the necessity of completely converting our highly customized information system software from mini-to microcomputer.

Electronic Data Processing

In vitro inhibition of IL-2 biosynthesis in activated human peripheral blood mononuclear cells by a trauma-induced glycopeptide.

Traumatic injury often results in profound immunopathology that can lead to immunosuppression, thereby increasing the morbidity and mortality due to sepsis. The isolation and partial characterization of an immunosuppressive glycopeptide (SAP) from serum of severely burned patients has previously been reported by our laboratory. Recently, this trauma peptide has also been identified in the serum of patients with multiple blunt trauma. This glycopeptide is capable of suppressing neutrophil chemotaxis, T-cell blastogenesis and the lysis of human erythrocytes. We demonstrate in this report that SAP inhibits interleukin 2 (IL-2) biosynthesis by mitogen-stimulated peripheral blood mononuclear cells. Peptide concentrations of 50 nmol and above significantly inhibited IL-2 production. Inhibition was not reduced by the addition of indomethacin or anti-PGE2 to cultures containing greater than 100 nmol of peptide, suggesting that inhibition is not entirely prostaglandin-mediated. Preliminary studies have shown that IL-2 suppression by SAP can be partially reversed by the addition of calcium ionophore. These results suggest a potential immunosuppressive mechanism of the trauma peptide in which T cell blastogenesis is inhibited by interference in IL-2 biosynthesis.

Calcimycin

Mini-micro-mainframe computer marriage: combining technologies in a radiology results reporting system.

The minicomputer-based information system in the Department of Radiology at the Medical College of Georgia Hospital and Clinics was placed in service in February, 1982. This system represents a sizable investment in minicomputer hardware in addition to more than 6 years of software customization. One serious deficiency in the original system was the lack of a radiology results reporting facility. Several options were considered to provide the department with this capability. The most obvious option was retiring the existing system and replacing it with one of a number of commercial products already offering results reporting. In-house development of a reporting facility lent itself more readily to microcomputers than to the existing minicomputer system. Due to system customization, economic and time constraints, it was decided to merge an in-house developed microcomputer-based report module into our existing minicomputer system. The minicomputer was able to communicate with and transfer files to and from both micro and mainframe systems. Combining technologies allowed us to continue taking advantage of our sizable investment in money, time, and customization while providing a microcomputer-based report module. Radiology reports are now typed on microcomputer word processors and bulk transferred to the minicomputer. The minicomputer provides access to both unapproved and approved reports on system terminals throughout the department. It also enhances reports by merging patient demographics and registration information. Using existing communications facilities to the hospital mainframe system, reports are provided throughout the institution.

Computer Communication Networks

The Nottingham study of neurotic disorder: comparison of drug and psychological treatments.

210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least.

Adult

The Nottingham ECT Study. A double-blind comparison of bilateral, unilateral and simulated ECT in depressive illness.

Sixty nine patients took part in a double-blind study to investigate the efficacy of bilateral, unilateral, and simulated ECT in the treatment of depressive illness. The findings suggest that both bilateral and unilateral ECT are highly effective treatments for depression and are significantly superior to simulated ECT. There was also evidence that patients receiving bilateral ECT recovered more rapidly than those receiving unilateral ECT and required significantly fewer treatments. The relevance of these findings to clinical practice is discussed.

Clinical Trials as Topic

Hearing loss in very low birthweight infants treated with neonatal intensive care.

The hearing of 111 perinatal intensive care survivors of birthweights 1500 g or less was assessed at a mean age of 6 1/2 years (range 4--12). These 111 infants included 86% of the long-term survivors of this birthweight cared for in the newborn unit of University College Hospital, London, during the years 1966--72. All these infants were nursed in commercially available incubators for periods ranging from 2 to 80 days (mean 37) in which the mean noise threshold was 65 dB. Ten (9%) had sensory neural nearing losses, one (1%) infant had a congenital conductive hearing loss, and 21 (19%) infants had exudative otitis media with a mean loss of 25 dB. Apnoeic attacks in the neotal period were the most significant predictors of hearing loss in these infants (P less than 0.05) and an indirect serum filirubin level of at least 170 micromol/l (10 mg/100 ml) in the neonatal period had an additive effect (P less than 0.05). There was no evidence that ambient noise had affected the hearing of these very low birthweight infants.

Apnea

Outcome for infants at high risk of major handicap.

Perinatal intensive care had been introduced in University College Hospital, London, by 1966. In the succeeding 10 years, 28-day mortality rates fell among infants of birth weight 1500 g or less. Among the survivors, the incidence of major handicap was 10% or less and the mean IQ increased to within the range expected for a normal population. Of the children aged 8 years or more 76% had no handicaps and were attending normal schools; 18% had minor handicaps or problems for which they were receiving extra help in normal schools; and only 6% were attending special schools. Throughout the 10 years of the study, the overall prognosis for these infants of very low birth weight improved significantly. Results among other high-risk groups were equally encouraging. Analysis of variance of the data from the infants who weighed 1500 g or less at birth indicated that perinatal complications, particularly illnesses associated with abnormal neurological signs or acidaemia in the infants around the time of birth, were the principal factors determining the condition of the survivors at follow-up. Thus, it is likely that additional refinements in the management of the perinatal period may result in further improvements in the prognosis of these and other high-risk newborns.

Achievement