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Biomedical subjects

J P Vestey

Publications and source records attributed to J P Vestey.

At least 19 recordsLinked to original sources

Sudden deepening of pigmentation during haemodialysis due to severe haemolysis.

A 37-year-old woman with chronic renal failure developed pain in the right flank during haemodialysis followed by rapid and dramatic deepening of pigmentation. Investigation indicated that the cause was severe haemolysis most probably due to mechanical damage to red blood cells passing through a stenosis in a dialysis blood line. Severe haemolysis should be suspected in subjects who suffer rapidly increasing pigmentation during dialysis. Such severe haemolysis should be recognized and treated rapidly since it may produce life-threatening systemic problems.

Acute Disease↗

Immunomodulation at the initiation of phototherapy and photochemotherapy.

The numbers and function of circulating lymphocyte subsets are within normal ranges in patients with psoriasis and are not affected by 4 weeks of ultraviolet (UV) therapy, except for a suppression in natural killer (NK) cell activity. However, it is possible that immunomodulation might occur at the initiation of phototherapy with a return to control values on more prolonged UV exposure. Thus, in this study the responses of 15 patients with chronic plaque psoriasis undergoing broad-band UVB therapy, 10 narrow-band (311-313 nm) UVB therapy and 10 PUVA therapy were compared. In each case, samples were taken immediately before starting treatment and 1 week later. Broad-band UVB and PUVA therapy had no effect on NK activity, but a significant reduction was found in the group receiving narrow-band UVB. In vitro lymphoproliferative responses to mitogens and to herpes simplex virus antigens did not alter with therapy, except there was a significant increase in mitogen responses (at optimal mitogen concentrations only) in the narrow-band UVB group. Generally no alterations in overall percentages of circulating mononuclear cells were found in any group. Samples were taken from the epidermis of the forearm and back of the patients receiving narrow-band UVB for the quantification of urocanic acid (UCA) isomers. The total UCA concentration remained unchanged after 1 week of therapy, while the percentage of cis-UCA increased significantly at both sites in the majority of patients. However, this rise did not correlate with the decrease in NK cell activity and the two parameters may not be related causally.

Adult↗

Immune responses of patients to orf virus infection.

Orf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to humans, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell-mediated and humoral immune responses to naturally acquired orf virus infection in humans. Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by ELISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40-kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virus infection was similar to that previously reported for sheep. Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antigens.

Adolescent↗

Primary nodular cutaneous amyloidosis--long-term follow-up and treatment.

A case of facial primary nodular cutaneous amyloidosis is reported. This illustrates: the striking appearance of this unusual condition; the investigations appropriate to establish the diagnosis and to exclude underlying systemic amyloidosis or a condition which might contribute to amyloidosis; and the difficulty of successful management. Initial investigation failed to reveal any evidence of systemic amyloidosis or an associated internal illness. Two amyloid nodules were excised, but 7 years later the patient developed further nodules on the adjacent facial skin and again sought dermatological advice. He was reinvestigated and again no underlying condition was found. A trial of cryotherapy was unsuccessful, but curettage and cautery produced a cosmetically acceptable result.

Adult↗

Major histocompatibility class II antigen expression on the surface of epidermal cells from normal and ultraviolet B irradiated subjects.

The influence of ultraviolet B irradiation in therapeutic doses on MHC II-positive epidermal cell numbers and their surface MHC II antigen expression was studied quantitatively using light microscopic immunoperoxidase and immunogold electron microscopic techniques. In multiple ultrathin sections through many MHC II-positive epidermal cells from five healthy subjects, prior to ultraviolet exposure, Langerhans cells and indeterminate cells were found to express similar densities of surface MHC II antigens, which were uniformly distributed over the cell surface. The variation in surface MHC II antigen expression on 97 dendritic epidermal cells from one subject was normally distributed. Following a 6-week course of ultraviolet B irradiation, in the same doses as those normally used for the treatment of psoriasis, MHC II-positive epidermal cell numbers were significantly reduced (mean decrease to 51% of the pre-UVB sample; p < 0.001 analysis of variance), but their surface MHC class II antigen density was significantly increased (p < 0.05 analysis of variance). No MHC II-negative Langerhans cells were detected in either the pre- or post-UVB samples.

Adult↗

Effect of phototherapy and urocanic acid isomers on natural killer cell function.

Ultraviolet (UV) radiation suppresses a variety of immune responses but it is uncertain whether this action contributes to the effectiveness of phototherapy. Urocanic acid (UCA) has been proposed as a mediator of the immunologic effects of UV. On exposure the naturally occurring trans-isomer of UCA in the skin changes into the cis-isomer, which has been demonstrated to mimic many of the immunomodulatory effects of UV irradiation. Natural killer (NK) cells play an important role in several immunologic processes and published evidence indicates that their activity is altered by UV irradiation. To ascertain the effect on NK cells of phototherapy used in the treatment of psoriasis, modulation of NK activity in psoriatic patients undergoing broad-band UVB, narrow-band UVB, or psoralen plus (PUVA) regimens was examined. This was compared with NK cell activity in psoriatic patients treated with topical coal tar and in normal subjects receiving broad band UVB. The NK cell activity of psoriatic and normal subjects was the same over a wide range of effector to target cell ratios. Almost all patients undergoing phototherapy exhibited depressed NK cell activity during or after irradiation, although the timing of the depression varied between the lamps used and may be related to dose. However, patients treated with topical coal tar showed unchanged NK cell activity throughout the therapy. The effect of UCA isomers on NK cell activity in vitro was also determined. It was found that cis-UCA induced a dose-dependent suppression of NK cell activity in both patients and normal subjects, whereas trans-UCA had hardly any effect in either group. Thus it is possible that there may be a correlation between cis-UCA formation in the epidermis and the modulation of NK cell activity that occurs during phototherapy.

Adult↗

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

Drug Administration Schedule↗

The effect of UV therapy on immune function in patients with psoriasis.

Ultraviolet radiation (UVR) is known to suppress some cell-mediated immune responses to antigens encountered during or soon after exposure. Phototherapy is widely used in psoriasis, and this study was undertaken to monitor changes in a range of immunological parameters during standard courses of treatment, with the aim of ascertaining whether such modulations contribute to the effectiveness of therapy. The responses of 17 patients with psoriasis undergoing UVB therapy, and four receiving PUVA therapy, were compared with 15 patients receiving coal tar treatment and four normal subjects undergoing UVB irradiation. In each case, samples were taken before starting therapy, after 4 weeks of therapy, and 4 weeks after completion of treatment. Serum immunoglobulin isotypes and complement components were within normal ranges in most of the psoriasis patients, and remained unchanged throughout therapy. Similarly, percentages of subsets of peripheral blood mononuclear cells (PBMC) were normal, and were unaltered by treatment. Patients who were already infected with herpes simplex virus (HSV), as demonstrated by a positive lymphoproliferation test in vitro, were monitored for asymptomatic HSV shedding and HSV recrudescences during therapy. There was little evidence that phototherapy caused reactivation of the virus. No significant alteration in lymphoproliferative response to HSV and to the mitogen concanavalin A was observed during therapy. Epidermal cells and blood adherent cells were used to present HSV to PBMC, depleted of adherent cells and enriched for T cells, in a lymphoproliferative assay. The functional antigen-presenting ability of adherent cells remained unchanged throughout therapy, whereas that of epidermal cells was suppressed during UVB irradiation and recovered, in most instances, after UVB therapy had been completed. The epidermis of patients with psoriasis contained about three times the quantity of urocanic acid (UCA) of normal subjects, whereas the UCA concentration in suction blister fluid did not differ between the two groups. During UVB irradiation, the percentage of cis-UCA rose in both the epidermis and suction blister fluid of all subjects, and it remained elevated in the blister fluid after therapy had finished. Tumour necrosis factor-alpha was measured in suction blister fluid, and its concentration did not alter consistently as a result of therapy. Whether any of the immunological parameters measured, and the changes noted, contribute to the effectiveness of phototherapy in the treatment of psoriasis remains uncertain.

Adult↗

Dermatitis herpetiformis and established coeliac disease.

Fifteen (5.3%) of 282 patients with dermatitis herpetiformis (DH) were diagnosed as suffering from coeliac disease before the onset of their DH. This group showed a female preponderance, and a later than usual onset of DH. The mean age at which DH developed was 40.0 years, and there was a mean interval of 13.2 years between the two diagnoses. Seven patients had stopped their gluten-free diet, and a further four were poor compliers. Persistent gluten ingestion in coeliacs with a specific genetic predisposition may result in the development of DH.

Adolescent↗

Disseminated metastatic cutaneous Crohn's disease.

Metastatic cutaneous Crohn's disease, in which noncaseating granulomatous infiltration of the skin occurs at sites separated from the gastrointestinal tract by normal tissue, is the least common dermatological manifestation of Crohn's disease. We report the case of an 18-year-old man who developed very widespread metastatic cutaneous Crohn's disease 2 years after he had first developed mild oral and anal lesions. His gastrointestinal symptoms had been satisfactorily controlled for 18 months with sulphasalazine alone prior to his developing skin lesions. The cutaneous lesions responded rapidly to oral prednisolone which was tailed off over 5 months and then withdrawn. He relapsed 6 months later and now requires a low dose of oral prednisolone to control the skin lesions. The only complication of this therapy has been exacerbation of mild acne vulgaris.

Adolescent↗

Disseminated cutaneous granulomatous eruptions associated with myelodysplastic syndrome and acute myeloid leukaemia.

Two elderly male patients presented with similar, widespread, papular, granulomatous eruptions and developed myelodysplastic syndromes. The first showed histological features of diffuse granuloma annulare and had mild hypergammaglobulinaemia, slightly abnormal liver function and a leucoerythroblastic anaemia. He developed acute myeloid leukaemia (AML) secondary to a background myelodysplastic syndrome and was treated with combination chemotherapy during which his eruption settled; his AML and his skin are in remission 1 year later. The second developed a myelodysplastic syndrome and a similar rash with histological features of papular cutaneous sarcoidosis but no systemic abnormalities apart from mild hypergammaglobulinaemia, cutaneous anergy to multiple recall antigens and activation of circulating monocytes. He has remained well but his rash and myelodysplastic syndrome have persisted. These cases are interesting because of the striking similarity of their granulomatous eruptions and their associated haematological abnormalities. Patients with such disseminated, granulomatous cutaneous infiltrations should be investigated to exclude associated haematological abnormalities if there is any abnormality of their peripheral blood picture.

Aged↗

Helicobacter pylori serology in patients with coeliac disease and dermatitis herpetiformis.

AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia.

Adolescent↗

Cowpox/catpox infection.

A 19-year-old veterinary nurse developed a cowpox/catpox virus (CPV) infection of her right third finger following a scratch from a tom cat suffering from pneumonia. The clinical course and investigation of the infection are described and the differential diagnosis discussed.

Adult↗