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Biomedical subjects

P J Holt

Publications and source records attributed to P J Holt.

At least 19 recordsLinked to original sources
PubMed2001

Recalcitrant necrobiotic xanthogranuloma responding to pulsed high-dose oral dexamethasone plus maintenance therapy with oral prednisolone.

A patient with the rare condition necrobiotic xanthogranuloma was treated from 1992 to 1999 with multiple therapies, none of which was effective. Her disease was progressive, causing significant disability. In September 1999 a trial of high-dose pulsed oral dexamethasone with maintenance corticosteroids led to a substantial improvement in her condition.

Aged↗
PubMed2001

Severe cutaneous reaction to CS gas.

Tear gas is used throughout the World for control of riots and civil disobedience. CS gas as used by the UK police force is issued as a 'spray' and is 5% CS in methylisobutylketone (MIBK), a potent irritant. Assaults on police officers in forces issued with CS spray have fallen significantly over the past 3 years, whilst having risen in areas without it. Thus, CS gas appears to be an effective deterrent. However, significant cutaneous reactions can occur as a result of exposure. We report a severe contact dermatitis to CS gas to highlight the clinical features. The nature of CS gas and potential cutaneous adverse reactions are discussed.

Adult↗
PubMed2001

Transformation of 2,2'-bimorphine to the novel compounds 10-alpha-S-monohydroxy-2,2'-bimorphine and 10,10'-alpha,alpha'-S,S'-dihydroxy-2,2'-bimorphine by Cylindrocarpon didymum.

Whole-cell suspensions of Cylindrocarpon didymum were observed to transform 2,2'-bimorphine to the compounds 10-alpha-S-monohydroxy-2,2'-bimorphine and 10,10'-alpha,alpha'-S,S'-dihydroxy-2,2'-bimorphine. Mass spectrometry and (1)H nuclear magnetic resonance spectroscopy confirmed the identities of these new morphine alkaloids.

Ascomycota↗
PubMed2000

Cloning, sequencing and expression in Escherichia coli of the primary alcohol dehydrogenase gene from Thermoanaerobacter ethanolicus JW200.

The structural gene, adhA, for a thermostable primary alcohol dehydrogenase was cloned from Thermoanaerobacter ethanolicus JW200. Constitutive expression from its own promoter was observed in Escherichia coli. The nucleotide sequence of adhA corresponded to an open reading frame of 1197 bp, encoding a polypeptide of 399 amino acids with a calculated Mr of 43 192. Amino acid sequence analysis showed 67-69% identity with alcohol dehydrogenases from two archaeal species and 29-37% identity with bacterial type III alcohol dehydrogenases. This represents the first reported cloning of an alcohol dehydrogenase from a bacterial species that is both thermostable and active against primary long-chain alcohols.

Alcohol Dehydrogenase↗
PubMed2000

Facial cutaneous tuberculosis: an unusual presentation.

Periocular cutaneous tuberculosis is a rare occurrence. We describe a 75-year-old Caucasian woman with tuberculosis of the left periocular region which responded completely to standard antituberculosis therapy. We hypothesize this unusual presentation may be due to minor trauma followed by inoculation.

Aged↗
PubMed2000

Safety of neck rotation for ear surgery in children with Down syndrome.

OBJECTIVE: Seek information about spinal cord safety for children with Down syndrome positioned for ear surgery. STUDY DESIGN: Prospective consecutive patients, each serving as his or her own control. METHODS: Somatosensory evoked potentials were recorded from 17 children who were undergoing elective otolaryngological surgery. None of the patients had neurological symptoms or physical examination findings suggesting cervical spinal cord embarrassment. Specifically, muscle tone was normal or mildly reduced globally, consistent with Down syndrome, and deep tendon reflexes were normal and not appreciably different in the upper and lower extremities. On plain lateral radiographs obtained in the neutral, flexed, and extended positions, the patients' cervical spines were normal. RESULTS: When the anesthetized children had their necks placed in either right or left 60 degrees rotation, no significant change in somatosensory latency or amplitude was found. With more than 99.999% certainty, neurologically intact children with Down syndrome with normal plain cervical spine radiographs were not exposed to extra risks by 60 degrees neck rotation during surgery. CONCLUSION: Patients with Down syndrome who are neurologically intact and who have normal lateral neck radiographs do not appear at great risk with neck rotation.

Adolescent↗
PubMed1999

The peripheral corneal melting syndrome and psoriasis: coincidence or association?

The peripheral corneal melting syndrome (PCMS) is a rare disease consisting of marginal corneal thinning that can progress to perforation. The PCMS carries a grave prognosis and it is of vital importance that dermatologists are aware that this may be responsible for a painful red eye in a patient with psoriasis. We highlight the features of the PCMS developing in an elderly woman with long-standing psoriasis to increase awareness of its significance, and hypothesize that an association may exist between the two conditions. Only one previous report has been published in which the authors speculate on the possible association of this syndrome with psoriasis. That few other cases have been described is either a consequence of under-reporting by both ophthalmologists and dermatologists unaware of a link or because the relationship between the syndrome and psoriasis is genuinely coincidental.

Aged↗
PubMed1999

Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific up-regulation by tumour necrosis factor-alpha (TNF-alpha) in synovial fluid.

This study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1beta, IL-4, IL-6, IL-8, IL-10, TNF-alpha and transforming growth factor-beta (TGF-beta) isoforms for varying time points up to 72 h at 37 degrees C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-beta isoforms and TNF-alpha and down-regulated by IL-4 and IL-10, with no effect observed with IL-1beta, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-alpha and not TGF-beta isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-alpha.

Arthritis, Rheumatoid↗
PubMed1999

Corneal epithelial-specific cytokeratin 3 is an autoantigen in Wegener's granulomatosis-associated peripheral ulcerative keratitis.

PURPOSE: In a previous investigation it was demonstrated that circulating antibodies to a 66-kDa corneal epithelial antigen (BCEA-A) are associated with peripheral ulcerative keratitis (PUK) in patients with Wegener's granulomatosis (WG). The aim of this study was to identify BCEA-A. METHODS: The 66-kDa antigen was purified from a bovine corneal epithelial protein extract, using DE52 ion exchange chromatography. Purified protein was used to raise rabbit polyclonal antibodies. These antibodies were used to screen a bovine corneal epithelial cDNA expression library. Positive clones were purified and sequenced. Clones were identified by DNA sequence homology searches of the GenBank DNA database. RESULTS: A cDNA clone that demonstrated strong binding to both the rabbit polyclonal antibody and patient sera, showed 85% homology to rabbit cytokeratin 3 (K3). K3 is a basic cytokeratin specific to corneal epithelium. No bovine DNA sequence for K3 is available. However, bovine K3 is larger than rabbit K3, with a molecular weight of 66 kDa. Immunofluorescence using both patient sera and the rabbit antibody demonstrated a cytoplasmic binding pattern on human corneal epithelium. CONCLUSIONS: This evidence suggests that the 66-kDa autoantigen (BCEA-A) associated with PUK in WG is cytokeratin 3, and this may form the basis of a diagnostic/prognostic test.

Amino Acid Sequence↗
PubMed1998

Serum levels of vascular endothelial growth factor (VEGF) are markedly elevated in patients with Wegener's granulomatosis.

OBJECTIVES: Necrotizing vasculitis and granuloma formation are the predominant features of Wegener's granulomatosis (WG). We have investigated the importance of vascular endothelial growth factor (VEGF) in monitoring disease activity in WG. METHODS: Serum VEGF levels were determined in 23 patients with active WG, 21 healthy controls and 25 patients with urinary infection, by ELISA using commercially available antibodies to VEGF. RESULTS: VEGF levels were enormously elevated in patients with WG compared to both controls and patients with urinary infection (P < 0.0001). Of the 23 patients, 21 (91.3%) had VEGF levels above the cut-off value (3.3 ng/ml, calculated as the mean of the controls + 2 S.D.). Further analysis of the data showed that VEGF levels did not correlate with age, sex, incidence of classic antineutrophil cytoplasmic antibodies (c-ANCA) or duration of the disease (P > 0.05), but there was correlation with disease activity (r = 0.51, P < 0.01). VEGF levels were higher in patients with major compared to those with minor disease activity (P < 0.01). However, there was no significant correlation between VEGF levels and the Birmingham scores for vascular activity and damage. CONCLUSION: VEGF levels are raised in WG patients compared to normal controls and may be a marker of disease activity. Further studies on serial blood samples from a large cohort of patients with WG and other systemic vasculitides are needed to evaluate the specificity and usefulness of VEGF levels in monitoring disease activity.

Antibodies, Antineutrophil Cytoplasmic↗