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Biomedical subjects

S O'Loughlin

Publications and source records attributed to S O'Loughlin.

At least 19 recordsLinked to original sources

Mycosis fungoides--a review of the management of 28 patients and of the recent literature.

BACKGROUND: Mycosis fungoides is an uncommon cutaneous T-cell lymphoma characterized by malignant monoclonal proliferation of T-helper lymphocytes. Its course is variable with a potential for lymphatic and hematogenous involvement. We report the investigations, staging, treatment, follow-up, and outcome of 28 patients. This is the first such study reported from Ireland. METHODS: Twenty-eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years) were reviewed over 12 years in the dermatology clinic which assesses an average of 4500 patients per year. All mycosis fungoides patients were referred from their family physicians. The diagnosis was made in all cases from a combination of clinical findings, histology, and immunohistochemistry. TNM staging revealed 11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB (T3), and one at stage III (T4). RESULTS: The usual male preponderance was not found. Eight patients needed multiple biopsies to establish the diagnosis. Detailed investigations were not useful in the early stages. Patients were followed up over a 12-year period. Thirteen patients died as a result of cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and died, a feature reported in only 10% of patients at this stage. Five patients showed unusual features, including a long history prior to presentation, the development of the rarely reported bullous mycosis fungoides, and aggressive disease beginning at a young age. CONCLUSIONS: Mycosis fungoides is rare; we reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13 patients died. Two patients who died were unusual in that they rapidly progressed from stage IA disease; however, in the majority of patients with this stage, the prognosis is excellent. Detailed investigations were unhelpful in early stage disease. Close clinical follow-up is essential to identify disease progression.

Adult↗

Protein tyrosine phosphatase genes downregulated in melanoma.

Phospho-tyrosine levels are increased in melanoma, apparently consistent with reports of elevated protein tyrosine kinase activity. Some protein tyrosine kinases are encoded by oncogenes and have been implicated in melanoma genesis. Decreased protein tyrosine phosphatase activity may also increase phospho-tyrosine. Protein tyrosine phosphatase genes are candidate tumor suppressors and loss of expression may contribute to melanoma genesis. Here we survey protein tyrosine phosphatase expression in pigment cells. Protein tyrosine phosphatase genes were cloned by reverse transcriptase polymerase chain reaction using degenerate primers based upon conserved sequences within the phosphatase catalytic domain. Reaction products were cloned and sequenced: 118 and 113 partial protein tyrosine phosphatase products were isolated from normal melanocytes and melanoma cells, respectively. Northern blotting analysis was used to study expression of 15 protein tyrosine phosphatase genes. Expression of PTP-kappa and PTP-pi was absent or downregulated in more than 20% of melanoma cell lines and in some unmanipulated melanoma biopsies. These closely related enzymes are members of the 2B receptor protein tyrosine phosphatase family previously implicated in contact inhibition. Loss of protein tyrosine phosphatase expression may contribute to the abnormal tyrosine phosphorylation seen in melanoma; these genes are candidate tumor suppressors.

Blotting, Northern↗

Suspected skin malignancy: a comparison of diagnoses of family practitioners and dermatologists in 493 patients.

BACKGROUND: In the Irish health system, dermatology patients present to their family practitioner for diagnosis and treatment, and are referred to a dermatologist for a second opinion where diagnosis is in doubt or when there has been therapeutic failure. The level of expertise in dermatology amongst family practitioners varies considerably. AIM: To compare the diagnoses of general practitioners and dermatologists over a selected period in patients with a possible diagnosis of skin cancer. METHODS: Four hundred and ninety-three patients were seen by one of two dermatologists over a 1-year period at a rapid referral clinic for patients suspected by their family practitioners of having unstable or possibly malignant skin lesions; 213 of these patients had a diagnosis made on clinical examination by the dermatologist, while 264 had diagnostic or therapeutic biopsies performed; 16 patients defaulted on surgery. RESULTS: The diagnoses of the family practitioners agreed with the diagnoses of the dermatologists on patients diagnosed clinically in 54% of cases. Thirty-eight patients had histologically proven skin malignancy. These were diagnosed accurately by the referring family practitioner in 22% of patients, while the dermatologists made the correct diagnosis prior to biopsy in 87%. CONCLUSIONS: In over 50% of cases diagnosed clinically, the dermatologist and family practitioner agreed. Histologically proven skin cancers were diagnosed accurately in only 22% of cases by family practitioners, compared to 87% of cases by dermatologists. Specific areas of diagnostic difficulty for family practitioners include benign pigmented actinic and seborrheic keratoses, squamous cell carcinoma, and melanoma. Postgraduate education for family practitioners should be directed towards these areas of deficiency. Dermatologists had difficulty distinguishing pigmented actinic keratoses from melanoma.

Dermatology↗

Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair.

BACKGROUND: Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS: To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS: 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS: There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS: All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.

Adaptor Proteins, Signal Transducing↗

Persistent infection of the chin with an unusual skin pathogen (Streptococcus milleri): a sign of intraoral carcinoma.

Streptococcus milleri is a commensal of the oropharynx and gastrointestinal tract which is not generally associated with skin disease. We now report a patient who presented with a pustular mass of the chin with lower lip anaesthesia. He was initially thought to have sycosis barbae, but response to treatment was poor and lesional swabs repeatedly cultured S. milleri. After some delay, squamous cell carcinoma of the mouth, involving the mandible and overlying skin, was detected. We consider that the S. milleri either invaded through the tumour from the mouth or root canal or colonized the skin from saliva dribbled over the numb lower lip. Isolation of an unusual organism and numbness of the chin are features that should suggest the need for early radiography.

Aged↗

Idiopathic anaphylaxis.

Three cases of idiopathic anaphylaxis are presented. This condition represents a rare but important cause of collapse. The development of atrial fibrillation, reported here for the first time, may lead to diagnostic difficulties. Early recognition and treatment is essential and will result in a good prognosis.

Adult↗

The role of computed tomography and sonography in acute bullous pemphigoid.

We report acute bullous pemphigoid occurring in an elderly female patient in whom abdominal sonography and computed tomography (CT) examinations revealed the presence of occult hepatic and splenic metastatic deposits from a primary pancreatic carcinoma. In the majority of cases bullous pemphigoid is a self limiting auto-immune disorder occurring in the absence of systemic disease. An association with visceral malignancy has been described by previous authors but the role of computed tomography and sonography in diagnosing occult malignancy and the subgroup of patients with pemphigoid in whom this should be undertaken has not been highlighted.

Aged↗

Labial melanotic macule: a clinical, histopathologic, and ultrastructural study.

BACKGROUND: The labial melanotic macule (LMM) is a recently described pigmentary anomaly that may simulate malignant melanoma. OBJECTIVE: Our purpose was to define the LMM clinically, histologically, and immunohistochemically in a large group of patients. METHODS: We describe the clinical features of 36 LMMs in 29 patients (aged from 4 to 79 years, 4 male, 25 female) seen during the past 4 years. Histopathologic findings in 21 of these patients are discussed. Seventeen lesions were immunostained with HMB-45 monoclonal antibody, and electron microscopy was performed on eight lesions. RESULTS: The majority of patients were women and had solitary lesions on the lower lip with the mean age of onset of 30 years. Histologically prominent basilar hyperpigmentation accentuated at the tips of the rete ridges was present without atypia or nevoid formation. Immunohistochemical studies showed that all intralesional melanocytes were HMB-45 negative, supporting their benign nature. Ultrastructurally, numerous stage III and IV melanosomes clustered within basal keratinocytes and papillary dermal melanophages were found. CONCLUSION: The LMM is a clinically and histologically distinctive benign pigmentary anomaly.

Adolescent↗

A quantitative immunohistochemical evaluation of lentigo maligna and pigmented solar keratosis.

Pigmented solar keratosis (PSK) is sometimes clinically indistinguishable from lentigo maligna, a form of malignant melanoma in situ. Occasionally histologic diagnosis is also difficult. Accurate diagnosis is essential, as the treatment and prognosis for each condition differs considerably. To determine whether there was a significant overlap in the number of melanocytes in these sun-damaged skin lesions, or whether immunohistochemistry might be helpful in the differential diagnosis, the authors examined skin biopsy specimens from 26 patients with obvious lentigo maligna and 15 patients with PSK using 3 monoclonal antibodies (HMB-45, NK1C3, and vimentin) and 1 polyclonal antibody (S-100 protein). Formalin-fixed paraffin sections were immunostained with each of the above antibodies, and immunopositive cells per mm2 of epidermis were counted. The difference between lentigo maligna and PSK counts was statistically significant at a level of P < .0001; furthermore, there was almost no overlap between the two groups. The sensitivity for the diagnosis of lentigo maligna was high with all antibodies. However, HMB-45 had the highest sensitivity and the lowest false-positive rate and was visually most pleasing. Using a cut-off count of 60 cells per mm2 of epidermis, HMB-45 had a sensitivity of 96% and a 0% false-positive rate. In this study, lentigo maligna was easily differentiated from PSK. The real value of immunohistochemistry in the differential diagnosis of these pigmented lesions should be tested in a prospective study using cases that are difficult to diagnose by routine light microscopy.

Adult↗

Paraneoplastic pyoderma gangrenosum.

Pyoderma Gangrenosum (PG) is often associated with an underlying disease. PG as a paraneoplastic disease is illustrated by the presentation of four patients with malignancy of myeloproliferative origin and PG. An associated malignancy is found in approximately 7% of patients with PG, most commonly haematologic in nature and in particular leukaemia. Clinically the PG is often of the superficial bullous variant and is associated with a poor prognosis.

Aged↗

HLA typing in Irish psoriatics.

Histocompatibility antigens were determined in 93 unrelated Irish psoriatic patients. The results were compared with the HLA profiles of 253 healthy unrelated Irish controls. There was a statistically significant increase in HLA B17 (P < 0.0001), B13 (P = 0.02), and B27 (P = 0.015) among the psoriatic patients. The frequency of HLAB8 (P = 0.002) and HLA B12 (P = 0.001) was lower than expected. When the subgroup of patients with psoriatic arthritis was evaluated separately, it was noted that the increase in HLAB27 was highly statistically significant (P < 0.0001). The relative risks of an Irish patient carrying the major psoriasis associated alleles of developing psoriasis are documented;-possession of the HLA B17 and B13 antigens conferring a risk of developing psoriasis vulgaris of 6.08 and 2.9 respectively. Further values for psoriatic subsets are presented. This is the first report of HLA typing in an Irish psoriatic population. The findings are discussed and compared with other population groups.

Arthritis, Psoriatic↗

Autobiographical memory and problem-solving strategies of parasuicide patients.

Recent research has noted the tendency of parasuicide patients to retrieve over-general autobiographical memories. Separate studies suggest problem-solving deficits within this group. The present study was concerned first with replicating these findings and, secondly, with developing a model of the relationship between over-general memory recall and poor problem-solving abilities in parasuicide patients. Anger and hopelessness were measured as markers for mood. In line with the hypotheses, the parasuicide group (N = 12) produced significantly over-general memories in contrast to a matched control group (N = 12). This occurred significantly in relation to positive cues, and latency to first responses was significantly delayed in the parasuicide group. The parasuicide group also provided fewer and less-effective problem-solving strategies than the control group, and a significant association was found between low effectiveness of problem-solving strategies and over-general memory recall in the parasuicide group. Anger and hopelessness levels were significantly higher within the parasuicide group in line with previous findings. The clinical implications of these findings are discussed.

Adaptation, Psychological↗

Familial non-diabetic necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a cutaneous disorder with distinctive clinical and morphologic characteristics. It is associated with diabetes mellitus in two thirds of cases. The aetiology and pathogenesis of NL are unknown but familial cases of NL seem to be extremely rare. We report the occurrence of NL in two sisters with normal glucose tolerance.

Biopsy↗

Polymorphic light eruption with contact and photocontact allergy.

We report a patient with long-standing polymorphic light eruption (PLE) who developed a photocontact allergy to mexenone and several contact allergies. The occurrence of multiple contact and photocontact allergies in PLE and the possible relationship of such allergies to the pathogenesis of PLE are discussed.

Aged↗