Biomedical subjects
Publications and source records attributed to C A Holden.
This paper details a UK consensus conference held in London in April 2000 to establish guidelines for the use of cyclosporin A for atopic dermatitis in children. It should be reserved for the severest refractory atopic dermatitis. In view of its potential toxicity, careful monitoring is mandatory, in particular blood pressure and renal function.
OBJECTIVE: To review 20 years of experience with sperm storage before vasectomy or before chemotherapy and/or radiation therapy (medical storage), and to evaluate its usefulness. DESIGN: Retrospective data analysis. SETTING: University-affiliated reproductive medicine clinic. PATIENT(S): Two hundred fifty-six men who underwent vasectomy and 258 men who underwent chemotherapy and/or radiation therapy. INTERVENTION(S): Review of patient clinical notes. MAIN OUTCOME MEASURE(S): The subsequent use of cryostored sperm and the number of pregnancies that resulted. RESULT(S): Only 4 of the 256 men who underwent vasectomy returned for treatment, and three pregnancies were achieved. Eighteen of the 258 men who underwent chemotherapy and/or radiation therapy returned for treatment, and six pregnancies were achieved. CONCLUSION(S): Only a small proportion of men (2%) returned to use their cryostored specimens after vasectomy, and pregnancy was achieved in most cases. Seven percent of men returned to use their specimens after chemotherapy and/or radiation therapy, and pregnancy was achieved in only one third of cases.
Somatic mutations within c-kit have been reported in individuals with mastocytoses, including urticaria pigmentosa (UP). We have identified three siblings with UP. We aimed to determine whether the c-kit proto-oncogene was playing a part in the aetiology of UP in these three siblings. Using seven microsatellite repeat markers spanning an 8-cM interval encompassing the c-kit gene we followed the transmission of the c-kit gene in this family. Furthermore, single-strand conformation polymorphism analysis was used to scan exon 17 of the c-kit gene for mutations in genomic DNA of all family members and somatic DNA extracted from skin of the eldest affected sibling, the proband. No mutations were found in exon 17 in either genomic DNA of all family members or somatic DNA of the proband. Patients with UP have been shown to possess somatic mutations of the c-kit gene. However, this locus has been excluded as playing a part in the three siblings examined here in whom a second gene locus must be determining their UP. Therefore, this study emphasizes genetic heterogeneity in UP. Future study to identify primary molecular determinants of UP should include affected sib-pair studies.
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BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon necrotising, non-infective ulceration of the skin. The management of PG is aimed at limiting tissue destruction, promoting the healing of the wound, and providing an acceptable cosmetic result. However, skin grafting is normally avoided because of the potential risk of pathergy-the localization of skin damaged by trauma. REPORT: We describe the use of split skin grafts in the management of ulcerative pyoderma gangrenosum in 4 patients. RESULTS: Our cases demonstrate that split skin grafts are a useful treatment modality in patients with ulcerative PG, producing a good cosmetic result. One case illustrates the importance of ensuring the disease is quiescent prior to grafting, to avoid pathergy. The other cases emphasise the need for prolonged immunosuppressive therapy to minimise the chance of reactivation of the disease process. CONCLUSION: Our preliminary experience of 4 cases of ulcerative PG indicates that split skin grafts have a role to play in its management. The ultimate cosmetic result is considered to be superior to allowing the wound to heal by secondary intention. To limit the risk of pathergy developing, our experience suggests a role for prolonged courses of immunosuppressive therapy. The most effective dose and duration of immunosuppressive therapy in patients with PG treated with split skin grafts remains to be determined. A controlled study would be of benefit to compare it with other current treatment options.
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Subcutaneous fat necrosis of the newborn (SCFN) is a relatively uncommon condition of the skin which is said to be benign and painless. We report an infant with extremely painful SCFN which was relieved only by opiate analgesia. SCFN normally resolves spontaneously within a few weeks. This case is, therefore, also unusual in that symptoms persisted beyond 6 months.
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OBJECTIVE: To report the fertilization rate and pregnancy results for intracytoplasmic sperm injection (ICSI) cycles using frozen-thawed epididymal spermatozoa. DESIGN: Retrospective analysis of consecutive ICSI cycles. SETTING: Tertiary referral center for infertility. PATIENT(S): Infertile couples in whom 39 patients (59 ICSI cycles) required the use of frozen-thawed epididymal spermatozoa. As no cycles were performed using fresh epididymal spermatozoa, outcomes were compared with those of 130 couples (170 ICSI cycles) using fresh ejaculated spermatozoa for severe oligoasthenozoospermia-teratozoospermia, in which < 200,000 motile spermatozoa were retrieved after Percoll density gradient centrifugation. INTERVENTION(S): Epididymal sperm aspiration during microsurgery, followed by ICSI. MAIN OUTCOME MEASURE(S): Fertilization, embryo cleavage, ET, and clinical pregnancy rates (PRs). RESULT(S): A total of 484 metaphase II oocytes were injected with frozen-thawed epididymal spermatozoa, resulting in a two-pronuclear fertilization rate per injected metaphase II oocyte of 47%, significantly lower than in cycles using fresh ejaculated spermatozoa (73%). Embryo implantation rates (12.0% versus 13.3%) and clinical PRs per transfer (18.4% versus 27.0%) were not different. When the prefreeze vitality was > 20%, compared with lower vitality, both the fertilization (56% versus 22%) and embryo cleavage (91% versus 57%) rates were significantly greater. CONCLUSION(S): The routine collection and cryopreservation of epididymal spermatozoa at microsurgery allows multiple ICSI treatment cycles with success rates similar to those of ejaculated spermatozoa. However, when the vitality of aspirated spermatozoa is < 20%, the poor fertilization rates indicate the need to consider an alternative source of viable spermatozoa.
Substance P has various immunomodulatory effects, including in vitro modification of lymphocyte proliferation and cytokine release. Elevated levels of substance P and increased staining of substance P-positive nerve fibres have been reported in atopic dermatitis patients. We examined fluoresceinated substance P binding to a range of lymphocyte subsets and compared the results in atopic dermatitis, non-atopic psoriasis patients and normal controls. Fluoresceinated substance P and phycoerythrin-labelled monoclonal antibodies to CD3, CD4, CD8, CD57, CD19 and CD14 were incubated in duplicate with Ficoll-Hypaque separated peripheral blood mononuclear leukocytes. With flow cytometry the fluoresceinated substance P-positive cells were identifiable as a peak of positively fluorescent cells, and the percentages of positive cells were measured. We have demonstrated binding of fluoresceinated substance P to all subsets examined, with significantly less binding to atopic dermatitis CD3-, CD8- and CD57-positive cells. This may affect cytokine release and hence be important in the pathogenesis of atopic dermatitis.
A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.
Many variants of bullous pemphigoid have been reported, some of which are clinically very atypical. One of the rarest variants is pemphigoid nodularis. We report three patients with this distinct entity. In all three cases patients initially presented with prurigo-like lesions and in one case nodular lesions preceded the onset of blistering by many months. Direct immunofluorescence was positive in all cases, with linear basement membrane zone deposition of IgG and C3. Circulating IgG antibasement membrane antibody was detected in two cases, and in these two patients on salt-split immuno-fluorescence the antibodies bound to the roof of the bullae.
We report a 25-year-old male with fever, generalized lymphadenopathy and an erythematosus maculo-papular eruption affecting face and upper body. A diagnosis of Kikuchi disease (necrotizing histiocytic lymphadenitis) was made on lymph node histology. The patient was found to be positive for the human T-cell leukaemia lymphoma virus (HTLV1). Kikuchi disease has been reported in association with infections such as Epstein-Barr virus (EBV), herpes (HHV6) and toxoplasmosis, but to our knowledge this is the first case of Kikuchi disease associated with HTLV1.
We describe a patient with angiosarcoma of the scalp arising in an area of radiodermatitis caused by X-ray epilation therapy for scalp ringworm as a child. Radiotherapy has been well documented as a causative factor in the formation of cutaneous malignancies, most notably basal cell and squamous cell carcinoma, but only rarely angiosarcoma. This is now the first reported case of angiosarcoma arising after X-ray epilation therapy for scalp ringworm, and we postulate a causative link between the two events.
The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) are present in the nerve endings in the skin and SP is thought to be present at abnormal concentrations in atopic dermatitis (AD) patients. Th1 and Th2 imbalance in AD has been the focus of recent immunological investigations and a preferential Th2 response by atopic cells on stimulation has been proposed. We wished to establish whether neuropeptides acted on T cells to affect their cytokine profile directly, using an accessory cell-independent stimulus (anti-CD3 monoclonal antibody and neuropeptides at several concentrations. We found that interferon (IFN)-gamma and interleukin (IL)-4 release were lower in AD. SP had an enhancing effect on both IFN-gamma and IL-4 at physiological concentrations (10(-10)-10(-6) mol/L) in AD, which was significantly different from controls (P < 0.05). VIP had inhibitory effects over this range in AD and in controls. We conclude that these neuropeptides have a modest effect on T-cell cytokine release and that their action is not cytokine-specific.
Amelanotic lentigo maligna melanoma is rare, only 10 cases over the face having been reported to date in the English literature. In none of these was the diagnosis suspected clinically, being made in all cases only after histopathological examination. We now report an unusual additional case of this uncommon lesion, which quickly progressed from an amelanotic lentigo maligna to an invasive melanoma in a short space of time, and review the literature concerning this condition.
Superficial angiomyxomas are rare, benign, dermal and subcutaneous tumours. We describe a 12-year-old girl who presented with a nodular swelling in the midline of her scalp that had been present since birth. Histological examination revealed an ill-defined myxoid lesion within the dermis, comprising spindle cells, blood vessels and occasional multi-nucleate giant cells. Immunohistochemical staining was negative for S-100, cytokeratin and smooth muscle actin, but focally positive for CD34. Our patient is unusual in that the angiomyxoma was present at birth, which has not previously been described. The importance of screening patients with cutaneous myxomas for cardiac lesions is discussed.
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