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Biomedical subjects

C Hardman

Publications and source records attributed to C Hardman.

At least 19 recordsLinked to original sources
PubMed2004

Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene.

Progressive osseous heteroplasia (OMIM 166350) is a rare autosomal dominant condition that presents in childhood as dermal ossification and may progress deeper to involve subcutaneous fat and connective tissue. Recently, paternally inherited inactivating mutations in the GNAS1 gene on chromosome 20q13 have been implicated in the pathogenesis, although sporadic cases have also been reported. We report a 9-year-old British Chinese girl with progressive osseous heteroplasia resulting from a de novo missense mutation (W281R) in the GNAS1 gene. She is of small stature (0.4th centile) and started to develop skin lesions at the age of 9 months. These have been confirmed histologically as osteoma cutis. She is of normal intelligence and development and has no dysmorphic features. The GNAS1 gene exhibits imprinting and maternally inherited mutations have previously been shown to result in Albright's hereditary osteodystrophy (OMIM 103580) with pseudohypothyroidism type 1a, whereas paternally inherited mutations result in progressive osseous heteroplasia or the Albright's hereditary osteodystrophy phenotype with pseudopseudohypothyroidism (OMIM 300800). With only nine mutations of the GNAS1 gene reported so far in progressive osseous heteroplasia, this new mutation helps to extend further the genotype-phenotype correlation.

Child↗
PubMed2003

The use of transscleral cyclophotocoagulation with a diode laser for the treatment of glaucoma occurring post intracapsular extraction of displaced lenses: a retrospective study of 15 dogs (1995-2000).

The objective of this retrospective study was to evaluate transscleral cyclophotocoagulation (TSCP) using a diode laser for treating aphakic glaucoma that developed after intracapsular lens extraction (ICLE) had been performed for displaced lenses. Records of 15 dogs (21 eyes) were reviewed. The intraocular pressure (IOP) and the presence of vision were recorded at the time of ICLE and TSCP and at 1, 3, 6-9, 12 and 24 months post TSCP. The glaucoma was considered controlled if the IOP was less than 25 mmHg. The results indicated that the effectiveness of TSCP using a diode laser for treating aphakic glaucoma was of a short-term duration (1-3 months), with three patients needing repeat TSPC. In addition, adjunctive antiglaucoma medications were often required to maintain an adequately controlled IOP. Over the 24-month period the number of dogs requiring intrascleral prosthesis, intraocular gentamicin or enucleation, or that were lost to follow-up, increased.

Animals↗
PubMed2002

A case of childhood sarcoidosis.

Cutaneous sarcoidosis is rare in children. We report a case of a 5-year-old Bangladeshi girl who presented with fever, a papular eruption on the lower limbs and trunk, malaise, anorexia and weight loss. There was multisystem involvement with marked hepatosplenomegaly, generalized lymphadenopathy, parotid fullness and chronic uveitis. Pulmonary infiltrates were seen on the chest X-ray. Histology of a skin biopsy showed naked noncaseating granulomata and PCR for Mycobacterium tuberculosis was negative. A clinical diagnosis of sarcoidosis was made. The patient was treated with oral prednisolone (2 mg/kg per day). An excellent clinical response with resolution of the rash and improvement of extracutaneous signs was noted within 3 months and she remains well on low-dose prednisolone on alternate days. We discuss the presentation and management of sarcoidosis in children, and highlight the potential difficulty in differentiating this from disseminated tuberculosis.

Anti-Inflammatory Agents↗
PubMed2001

Non-M protein(s) on the cell wall and membrane of group A streptococci induce(s) IFN-gamma production by dermal CD4+ T cells in psoriasis.

Recently we have demonstrated that a disease-specific subpopulation of CD4+ T cells isolated from skin lesions of chronic plaque psoriasis produces interferon-gamma in response to group A streptococcal (GAS) antigens. To determine if these T cells recognize M or non-M protein, extracts from cell wall of type M6 GAS (M6W) and its isogenic M gene deletion mutant (M-W), M6 membrane extract (M6M) and recombinant M6 protein (rM6) were used to stimulate GAS-reactive T-cell lines from nine patients with chronic plaque psoriasis. T-cell lines were incubated with or without streptococcal extracts for 18 h in the presence of a transport inhibitor, stained for surface CD4 and intracellular cytokine expression, and analysed by flow cytometry. Variable numbers (0.2-34%) of CD4+ T cells produced interferon-gamma, in all but one of the T-cell lines tested, in response to M6W, M-W and M6M extracts. No significant difference between the response to M6W and M-W extracts was detected. In addition, rM6 protein failed to increase CD4+/interferon-gamma+ T-cell numbers in seven of nine T-cell lines compared to medium alone. For the group, there was a highly significant correlation between the responses to the three extracts (M6W vs M-W, P = 0.0005; M6W vs M6M, P = 0.0003; M-W vs M6M, P = 0.0001). Low or minimal numbers of interleukin-4- and interleukin-10-producing CD4+ T cells were occasionally induced. These findings suggest that a subpopulation of CD4+ T cells isolated from skin lesions of chronic plaque psoriasis patients produces interferon-gamma in response to non-M protein(s) present on the cell wall and membrane of GAS.

Adult↗
PubMed2001

Lichen myxoedematosus with associated cardiac abnormalities.

We describe a 42-year-old woman who developed lichen myxoedematosus. Twenty years after the onset of the disease she became breathless and hypertensive, and an echocardiogram showed a mass on the mitral valve, which was thought to be a mucin deposit. Her hypertension was resistant to treatment with combination antihypertensives. To our knowledge, this is the first report to link lichen myxoedematosus with a valvular mucinous mass. This case also demonstrates the slow clinical progression of the disease over 20 years.

Adult↗
PubMed2001

Phacofragmentation for morgagnian cataract in a horse.

A 3-year-old Paint gelding was presented for sudden onset of cataract affecting the right eye. Ophthalmic examination revealed subtle to mild microphthalmia and a mature cataract affecting the right globe. The right eye was treated with an antibiotic-corticosteroid ophthalmic ointment and phacofragmentation was recommended. On re-examination 5 months later, resorption of the cortex of the right lens and a morgagnian cataract were evident. The nucleus was positioned ventronasally in the lens capsule. The right eye had light perception, and a menace response was present. Examination of the right fundus via binocular indirect ophthalmoscopy was not possible. Ophthalmic ultrasonography revealed that the right globe was 4 mm shorter in axial length when compared with the left globe. There was a marked reduction in the size of the right lens vs. the left lens, and the presence of a moderate amount of hyperechoic debris was identified within the vitreal compartment of the right globe. Phacofragmentation, irrigation and aspiration of the morgagnian cataract and an anterior vitrectomy were performed. On postoperative examination, the eye was comfortable and a menace response was present. The horse regained useful vision and continues to have a comfortable, visual eye 7 months postoperatively.

Animals↗
PubMed2001

Diode laser transscleral cyclophotocoagulation for the treatment of primary glaucoma in 18 dogs: a retrospective study.

OBJECTIVE: To evaluate a higher total energy protocol for diode laser transscleral cyclophotocoagulation (TSCP) for the treatment of primary glaucoma in dogs. PROCEDURES: Diode laser TSCP was performed on 24 eyes of 18 dogs (six dogs were treated bilaterally). A glaucoma probe with a spot size of 600 microns was applied in 25 sites 3-4 mm posterior to the limbus for dogs. A power of 1000 milliwatts (mW) for a duration of 5000 milliseconds (ms) to deliver an average 125 J of energy per eye, which is higher energy delivery than previously reported for the diode laser for the treatment of canine glaucoma. Anterior chamber needle paracentesis was performed using a 30-gauge needle until intraocular pressure (IOP) was measured to be less than 15 mmHg by applanation tonometry. Subconjunctival corticosteroids were administered in all cases and a temporary tarsorrhaphy was applied in 13 of the 24 treated eyes. Postoperative topical and systemic corticosteroids, and carbonic anhydrase inhibitors were administered as required to maintain an IOP of less than 25 mmHg. Intraocular pressure was measured at approximately 3 h postoperatively then at 1, 2, 3, 7, 14, 28, 60, 120, and 180 days. Adequate control of IOP was considered to be less than 25 mmHg on re-examination. RESULTS: Intraocular pressure was successfully maintained within the normal range in 22/24 eyes (92%). Three eyes required a second diode laser treatment within the first week postoperatively. Two eyes developed recurrence of glaucoma at 8 and 32 weeks postoperatively. Follow-up ranged from 8 to 21 months. Fourteen eyes were assessed by clinical examination and history to be potentially visual. Of these, seven eyes (50%) regained useful visual function. Mean IOP at 6 months was 11.0 +/- 7.6 mmHg and at 12 months was 11.0 +/- 8 mmHg. Postoperative complications included cataracts (six cases), corneal ulceration (three cases), and keratitis (three cases). Of 13 cases that were treated postoperatively with a temporary tarsorrhaphy, only one case (8%) developed corneal disease. Of the remaining 11 cases that were not treated with a temporary tarsorrhaphy, there were three cases of corneal ulceration and two cases of vascular keratitis (45% incidence of corneal disease). This was found to be statistically significant (P < 0.05). Postoperative complications of hyphema and phthisis bulbi were not seen in this series. CONCLUSION: Low energy, higher power laser cyclophotocoagulation was effective in the treatment of canine primary glaucoma, with 50% of potentially visual eyes regaining vision, but may cause an increased incidence of secondary cataracts.

Animals↗
PubMed2001

Lateral canthoplasty for facial nerve paralysis and exposure keratitis in a mouse.

An 11-month old entire male mouse was presented with mucopurulent discharge and corneal scarring of the left eye. This mouse previously had a history of ear mites that responded to therapy, and had undergone surgery to remove a large discharging mass from the left side of the neck. The eye problem was noted prior to surgery, but after the ear mite infection. Examination revealed absence of a palpebral reflex in the left eye, and no spontaneous movements of the left ear or lip and whiskers. Examination of the left eye revealed extensive corneal vascularisation and pigmentation. Intraocular structures were not visible. A diagnosis of facial nerve paralysis and secondary exposure keratitis was made. Surgery was performed to close the lateral canthus and reduce corneal exposure. Following surgery the eye discharge ceased and corneal vascularisation resolved, however corneal pigmentation persisted.

Animals↗
PubMed2001

Radioactive gold-198 seeds for the treatment of squamous cell carcinoma in the eyelid of a cat.

A 19-year-old, speyed, domestic short-hair cat was presented with an eyelid tumour of 3 months duration. Ophthalmic examination revealed a large, raised, ulcerated and bleeding mass affecting the left lower eyelid. The mass was 12 mm x 10 mm in size, extended to the medial canthus and had eroded 10 mm of eyelid margin. Mandibular lymph nodes were not palpably enlarged. A diagnosis of squamous cell carcinoma was confirmed by histologic examination. Due to involvement of more than half the lower eyelid, it was decided that treatment with radioactive gold-198 seeds was appropriate. Nine radioactive gold-198 seeds were implanted, delivering a minimum tumour dose of 65 Gy. Three weeks postoperatively the mass had resolved, with only a small scab remaining. After a further 3 weeks, there was no evidence of the eyelid tumour. Although approximately 7 mm of eyelid margin was absent, this did not cause any clinical signs other than mild conjunctivitis. There was no evidence of the tumour 10 months postoperatively, when the cat was euthanased for unrelated disease.

Animals↗
PubMed2000

Testing Müllerian mimicry: an experiment with wild birds.

Experiments with wild birds feeding on pastry 'prey' were performed to test competing theories of Müllerian mimicry Conventional theories predict that all resemblances between defended prey will be mutually advantageous and, hence, Müllerian. In contrast, unconventional theories predict that, if there are inequalities in defences between mimetic species, the less well-defended prey may dilute the protection of the better defended species in a quasi-Batesian manner. This unconventional prediction follows from an assumption that birds learn about the edibilities of prey using rules of Pavlovian learning. We report on two experiments, each lasting 40 days, which showed that a moderately defended prey can dilute the protection of a better defended mimic in a quasi-Batesian fashion, but can add protection to a mimic which has the same moderate levels of defence. These results match predictions of unconventional theories of mimicry and go some way to resolving the long-running arguments over the nature of Müllerian mimicry.

Animals↗
PubMed2000

Skin CD4+ T cells produce interferon-gamma in vitro in response to streptococcal antigens in chronic plaque psoriasis.

Recently, we have demonstrated that group A streptococcal antigen reactive T cells are present in the skin lesions of chronic plaque psoriasis. To determine the cytokine profile (interferon-gamma, interleukin-4 and interleukin-10) of these T cells in response to streptococcal antigens, T cell lines were cultured from untreated lesional skin of 13 patients with chronic plaque psoriasis and 12 patients with other inflammatory skin diseases. T cell lines were incubated with or without a sonicated heat-killed mixture of group A streptococcal isolates for 18 h in the presence of a transport inhibitor, stained for surface CD4 or CD8 and intracellular cytokine expression, and analyzed by flow cytometry. Psoriatic T cell lines were grown from 10 of 13 patients and were predominately CD4+ (64%-85%) with 10%-32% CD8+ T cells. Variable numbers of CD4+ T cells produced interferon-gamma (0.8%-35%, median 13.9) in eight of 10 T cell lines (p < 0.02). In contrast, CD4+ T cells in five of 12 T cell lines obtained from disease controls did not produce or produced minimal interferon-gamma in response to group A streptococcal isolates; this was significantly different from the psoriatic T cell lines (p < 0.05). Small numbers of interleukin-10 positive (0.8%-1.3%) and interleukin-4 positive (2.1%-2.5%) CD4+ T cells induced by group A streptococcal isolates were also present in two out of five and three out of five psoriatic T cell lines, respectively. This was significantly less in each case than the numbers of CD4+/interferon-gamma+ T cells (p < 0.05). Cytokine-positive CD8+ T cells were rarely observed. These findings demonstrate that a subpopulation of CD4+ T cells in chronic plaque psoriasis skin lesions produces interferon-gamma in response to streptococcal antigens and may be relevant to the pathogenesis of psoriasis.

Adult↗
PubMed1997

Induction of cutaneous lymphocyte-associated antigen expression by group A streptococcal antigens in psoriasis.

The cutaneous lymphocyte-associated antigen (CLA) has been proposed as a homing receptor for the selective migration of memory T cells into the skin. To investigate the effect of group A streptococci (GAS) on the migration of T cells in psoriasis, CLA expression was assessed by double-staining for CD3 and the HECA-452 epitope on peripheral blood T cells from 13 patients with psoriasis, 10 patients with other inflammatory skin diseases and 12 normal controls before and after 7 days culture with a GAS sonicate, Candida albicans (control antigen) or medium. In addition, CLA+, and CLA-, CD3+ CD45RO+ subsets were isolated from individuals in each group and V beta 2 expression and proliferation to GAS studied. Mean CLA expression by freshly isolated T cells was almost identical in the three groups. After culture with GAS, T cells from the psoriatic patients and control showed a significant increase in mean percentage CLA+ expression compared to medium (P < 0.002, P < 0.05, respectively). This induction was inhibited by the addition of anti-IL-12 antibody. However, in psoriatic patients, but not in controls, the GAS-induced increase was significantly greater than that of C. albicans (P < 0.002) and was accompanied by a decrease in T cells positive for the peripheral lymph node homing receptor, L-selectin (P < 0.05). The percentage of V beta 2+ T cells was markedly higher in the CLA+ than in the CLA- T-cell subset in psoriatic patients (P < 0.01) and controls; both subsets proliferated to GAS, in each group. These findings suggest a differential modulation of specific tissue homing receptors on T cells by GAS in psoriasis.

Adolescent↗
PubMed1997

Differential T-cell reactivity to the round and oval forms of Pityrosporum in the skin of patients with psoriasis.

Pityrosporum yeasts have been implicated as a trigger for the initiation of scalp lesions in psoriasis. To determine whether Pityrosporum-reactive T cells are present in lesional psoriatic skin. T-cell lines (TCL) were cultured from the scalps of nine patients with psoriasis and seven with alopecia areata (disease controls), and from non-scalp lesions from six of the psoriatic patients. The psoriatic skin TCL were stained for CD3, CD4, CD8 and TCR alpha beta expression and tested in a proliferation assay with Candida albicans and purified protein derivative (PPD), and cytoplasmic and cell-wall extracts of P. ovale (oval) and P. orbiculare (round). The proliferative responses of corresponding peripheral blood mononuclear cells (PBMC) were also determined. All the PBMC samples responded to the Pityrosporum extracts to variable extents, but no significant difference in the response of the group to the two different forms of yeast was observed. The response was mediated by CD4+ T cells and inhibited by the addition of anti-HLA-DR antibody. In addition, all nine psoriatic scalp TCL, which were predominantly CD3+, CD4+ TCR alpha beta(+), responded to the cytoplasmic, and five of nine TCL to the cell-wall extract of P. orbiculare. In contrast, only three of the nine TCL proliferated to either extract of P. ovale. This difference was significant for both the cytoplasmic (P < 0.01) and cell wall (P = 0.01) extracts. Similarly, the TCL cultured from non-scalp psoriatic lesions also showed a more marked response to the P. orbiculare extracts (P = 0.05). Furthermore, four of seven and two of seven scalp TCL from lesions of alopecia areata responded to the P. orbiculare and P. ovale extracts, respectively; these responses did not differ significantly from those of the psoriatic scalp TCL. None of the skin TCL responded to either Candida albicans or PPD. These findings demonstrate that T cells with differential reactivity to the round and oval forms of Pityrosporum are present in, but are not specific for, psoriatic skin lesions. A role for these cells in the pathogenesis of psoriasis remains speculative.

Adult↗